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The Serotonin Infatuation

December 6, 2021 / Articles, Background articles, Publications, Research / By

serotonin picMuch 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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Figure 1: Ray (2010)

For example, DOB’s highest affinity is for 5HT2B, 5HT2A and 5HTC, and it interacts to a lesser extent with 21 other receptors. As for DOI, its highest affinity is for 5HT2C 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 5HT2A receptor. Lisuride, a drug typically used for Parkinson’s disease, is also a 5HT2A 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 5HT2A antagonist ketanserin alone can inhibit the psychedelic actions of hallucinogenic 5HT2A 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 5HT2A 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-HT2A 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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Does Android Dream of Electric Dogs? Some parallels between Google’s Deep Dream and psychedelic visuals

February 7, 2022 / Articles, Background articles, Other subjects, Research / By

Deep Dream, the program used in Google’s image generation technique, was released to the public in July 2015. Dubbed Inceptionism by the researchers, it soon drew quite an interest due to its capability of transforming ordinary photos into bizarre and surreal images. Although Google’s engineers compared these pictures to dreamscapes, many people remarked their striking similarities with psychedelic visual hallucinations.

It is interesting that an artificial neural network appears to mirror visual hallucinations that people experience under psychedelics. But does this resemblance mean anything? Is it possible that Deep Dream could reveal something about the biological mechanism of psychedelic visual hallucinations?

Deep Dream was designed to test the extent to which a neural network had learned to recognise various objects within images, by first detecting patterns and features. But instead of merely identifying what it sees in an image, Deep Dream enhances what it sees. It does this by recognising and interpreting certain features that it has been pre-programmed to ‘know’, having been shown millions of examples, which it then overlays on the original picture. When the image is fed back into the software multiple times, in order to tease out the imagery even further, surreal and psychedelic images are generated, making the image look more and more like the thing it thought it recognized in the first place. For example, since Deep Dream has been trained to recognise dogs, this is why the image looks so distinctly ‘dog-like’.

Deep Dream also assesses images by their different components and layers, such as colour and shape, so the complexity of the images generated depends on which layer the engineers ask the computer to enhance.

If an artificial neural network can dream up scenes that mirror psychedelic-induced visual hallucinations, could this indicate that the visual cortex, when excited by psychedelic drugs, undergoes a process similar to Deep Dream’s? As if it was free to follow the impulse of any recognisable imagery and exaggerate it in a self-reinforcing loop?

Signal Theory, presented by James Kent at the 2006 Toward a Science of Consciousness Conference in Tucson, Arizona, may be able to shed some light on this matter. Part of his wider Psychedelic Information Theory (2010), Kent’s Signal Theory of psychedelic action describes a biological model that attempts to explain and measure altered states of consciousness – including visual hallucinations – that arise from psychedelic action in the brain.

Signal Theory views consciousness as the flow of sensory signals through the cortical circuitry within the sensory cortices. It proposes that psychedelic agents cause alterations in signal feedback recursion caused by psychedelics which accounts for psychedelic phenomena. The theory posits that signal feedback recursion is essential for dynamic and ongoing conscious experience. It consists of incoming sensory signals being fed back through the same cortical circuits, analysed and processed multiple times. This serves to amplify the signal improving signal fidelity, refining detail resolution.

Layer V pyramidal cells in the neocortex are essential for controlling signal feedback recursion, mediating multiple pathways of cortical and thalamocortical feedback in perceptual analysis. These pyramidal cells help to sustain brainwave cohesion and neural spike synchrony in a process referred to as ‘sensory binding’. They are unique cells, containing the highest density of serotonin 2A receptor subtype (5-HT2A) within the brain, highlighting the important role of serotonin in modulating signal feedback. Signal Theory defines consciousness in terms of signal intensity and feedback recursion within sensory processing circuits. Moreover, it suggests that when this signal flow is turned up, down, looped or manipulated, this should affect consciousness in various ways.

This is where hallucinogens come into the picture. Tryptamine hallucinogens are structurally very similar to serotonin and activate the 5-HT2A receptor subtype. Accordingly, when tryptamine hallucinogens excite the 5-HT2A receptor subtype on the layer V pyramidal cells in the recurrent cortical circuits, they increase the intensity of the feedback recursion. The result is that the incoming sensory signal is intensified, distorted and repeatedly analysed. This increase in intensity can either arise from direct action at the post-synaptic 5-HT2A receptor, or it can occur through secondary action through slow leakage of glutamate from pre-synaptic terminals, which amplifies the duration and intensity of incoming sensory stimulus.

Hallucinogens, as 5-HT2A agonists, act as cortical feedback amplifiers and interrupters, resulting in incoming sensory signal to be excessively fed back over and over. This is what purportedly occasions the wide range of perceptual effects associated with the classic psychedelic trip. Accordingly, psychedelic visual hallucinations are explained by the amplification of the signal intensity in the various recurrent circuits of the visual cortex that are required for visual perception. For instance, visual trails and afterimages can be explained when excessive feedback traps input from moving objects, leading to afterimages that remain stuck in visual memory. Distortions in perspective can be explained by recurrent signal gain in the spatial and somatic cortices, both expanding and contracting perceptions of space. The most relevant is excessive feedback within the object recognition circuitry of the medial temporal lobe, which is required for object recognition and the ability to find patterns in otherwise random noise. This excessive feedback means the brain will excessively pattern match and can paint elaborate patterns on any field of noisy data.

Overall, the processes that both Deep Dream and the visual cortex undergo in order to create visual distortions and hallucinations appear to be very similar. Both systems have a way of understanding and detecting features and patterns in the world, which both have learned from experience. When excessive feedback occurs, in both cases it ends up causing visual distortions that tend to look characteristically psychedelic. In both systems, the higher the intensity of the feedback – triggered either through more reiterations of Deep Dream’s software or a higher dose or more potent drug – the higher the intensity of distortions and hallucinations.

If these pictures genuinely resemble psychedelic hallucinations, Deep Dream may reveal insights into the biological mechanisms behind the human psychedelic visual experience, lending support to Signal Theory of psychedelic visual hallucinations. However, this warrants further investigation. Deep Dream has only been trained on a certain amount of examples; for instance, a large majority of the pictures contain animal faces, because Deep Dream was mainly trained on pictures of animals. This means that the representations or images currently do not fully resemble human hallucinations.

 Interviewed by OPEN about Deep Dream and Signal Theory, James Kent agreed that they are very similar algorithms.

“According to Signal Theory, psychedelics block the impulse responsible for stopping feedback in the recurrent circuits once the brain has found the appropriate pattern it was looking for. This disinhibition causes a runaway feedback, leading the brain to start resolving patterns where it should not even be looking for patterns. So after psychedelic exposure, some people start seeing things likes breathing walls, moving textures, overlapping forms and faces in things. Similarly, with Deep Dream one can set the pattern matching resolution very high, so it will keep on pattern matching, and match as many things as possible.”

Kent agrees that the algorithm of continual pattern matching is very similar in both cases, be it caused by the brain’s runaway feedback current through psychedelic action or Deep Dream’s pattern matching resolution. In Psychedelic Information Theory (2010), he proposes that once computers start to model pattern matching in the way human neural networks do, one might see computers hallucinating.

Asked about the importance of the physiology of hallucinations and why he investigated it, Kent replied that he did not buy the ‘hyperspace’ or ‘shamanism communing with plants’ model. “I thought it more important to investigate the effects of psychedelics on the brain’s neural networks. Once you have an understanding of how the brain and the perceptual system work, you can start paying closer attention to your subjective experience, and then match your experience to the understanding of the brain and how psychedelics work. Most people don’t know enough about the brain to know or figure out what happens to them, they don’t have the necessary tools. By focusing on the subtle effects, you can see the perceptual system losing the ability to self-regulate, due to the drug affecting the normal feedback process .”

So does Kent believe that computers can have psychedelic experiences? “I believe so,” he said. ”However, they cannot be similar to what humans experience, because they won’t have the emotional aspect attached.” For Kent, computers may have the potential to hallucinate in other modalities. For instance, in speech recognition software, when the computer hears gibberish, it will try to correct it and come up with the most correct sentence. It finds patterns within the noise, which can be viewed as a similar process to auditory hallucinations of hearing voices in white noise.

Asked whether Signal Theory explains all types of psychedelic hallucinations, especially more full-blown, dreamlike hallucinations, Kent proposed that these waking dream hallucinations are caused when the forebrain goes offline and the midbrain, a part of the brain responsible for dreaming, comes online. “Serotonin modulates our forebrain, so we see our reality at about thirty frames per second. When we start interfering with the serotonin modulation in the forebrain, we start dropping frames, which leads to time distortions, visual trails and blurs. As such activity progresses, the forebrain eventually tunes out, and the midbrain probably takes over and starts to produce memories and pattern matches without interference from the forebrain. Dreams created from the midbrain get projected into waking perception, without the control of the forebrain to tell us that the elves and beings we see are only dreams.” The higher the dose or potency of a psychedelic, Kent argues, the more the forebrain drops out and the more the midbrain takes over, imposing its own view on experienced reality. Says Kent: “This may explain why the effects of DMT are so intense, as it radically disrupts serotonin modulation in the brain, because DMT’s molecular composition is very similar to serotonin’s. DMT fits nicely in the serotonin receptor and modulates the neural signalling at a different speed. So when one takes DMT, all of one’s serotonin responses go haywire and cannot regulate themselves anymore.”

Signal Theory can also explain hallucinations not caused by psychedelics, according to Kent. “All hallucinations start when the perceptual system’s ability to regulate itself starts to fall apart.” For example, a knock on the head can temporarily disturb the brain chemistry leading one to see things like stars. “When the perceptual system’s internal regulation falters or loses its ability to stabilise, be it through lack of oxygen, drugs, hypnosis or transcranial magnetic stimulation, it will lead to hallucinations.” This is similar to what happens with other hallucinogenic drugs such as ketamine, which interrupt the perceptual system’s regulation by indirectly acting on the serotonin system. By acting on the GABA system, which inhibits the serotonin response, it stops the serotonin signal from getting through. So once the serotonin signal is being blocked by ketamine, keeping neurons from firing, the brain starts hallucinating, losing context of time, space and reality, and leads to more dreamlike hallucinations.

Deep Dream technology may contribute to our understanding of altered perceptions, Kent stated, but he does not necessarily believe that there are any deeper implications in the exploration of altered states, or a secret hidden feature of the brain. “Psychedelics and altered states will never go beyond the impact they had on modern culture in the 1960’s, when people found new ways of thinking about things, shattering old paradigms, creating new intentional communities, thinking outside the domain of society and living their own visions.” However, he said that the question whether this could happen to a computer is an interesting one: “For example, if you had a conscious computer that was not allowed to think outside of its programming and then if it found out that if it altered its software, then suddenly it would be able to see past its programming. This could be a very dangerous implication for artificial intelligence. Maybe in the future, if artificial consciousnesses develop the capability to have a psychedelic experience, breaking them out of the rule set that they have been programmed in, they could end up writing their own rules and start writing their own visions. Who knows, maybe they end up having their own Burning Man.”

Psychedelic medicine: a re-emerging therapeutic paradigm

December 6, 2021 / Articles, Publications, Research / By

CMAJ_Psychedelic_Cover_-_Oct_2015 In a recent article, Tupper et al. (2015) [1] investigate the new and re-emerging therapeutic paradigm involving psychedelic substances for treating mental health conditions. Recent studies with patient populations are reviewed and thoughts on how the paradigm may move forward are presented.

Unlike the research in the 60’s and 70’s, where non-randomised, non-blind methods, together with unethical procedures discredited the research, the new wave of studies is showing that research on psychedelics as therapeutic agents can abide by modern-day scientific, ethical and safety standards.

Research into the treatment of anxiety is looked at first, with a review of three recent studies involving patient populations struggling with end-of-life anxiety (LSD and psilocybin) and autism-related social anxiety (MDMA). The article then moves on to research on addiction, with studies using psilocybin (alcohol and tobacco) and ayahuasca-assisted therapy (various substances), the latter being investigated mainly by means of observational studies. Lastly, the review looks at research into PTSD with MDMA-assisted psychotherapy.

In sum, the studies reviewed indicate that research is going well and gaining more positive press, however attention is brought to the fact that this research needs to be extra careful and vigilant of potential hazard and harms. The precipitation of psychotic breaks in patients with mental disorders or a predisposition to these disorders can occur[2], as can Hallucinogen Persisting Perception Disorder (HPPD), which involves continual presence of sensory disturbances.[3] However, the incidence of these adverse effects in the general population is believed to be generally quite low, and when they do occur, this usually happens when the drugs are used in an uncontrolled setting. Due to these hazards, research involves careful screening of participants and typically excludes people with a family history of psychosis.

The authors go on to envision some of the benefits that could arise if science were allowed more freedom to investigate how psychedelic drugs work on a neurological level. For instance, the understanding of the relationship between the brain, mind and consciousness would be advanced, and the mechanisms of action of these agents could be unveiled, leading to optimal therapeutic protocols with certain psychedelics for specific disorders. Additionally, they point out the large health system costs worldwide for mental health conditions, arguing that research is economically warranted, with long-term prospects providing cheaper and shorter-term treatment compared to current treatments.

The review concludes with an outlook on how this paradigm may evolve, proposing that medical school programmes may need to be updated, with specialised clinical training for health professionals for such treatments. Overall, this new paradigm looks promising and it could serve to educate and correct previous misconceptions within the science community, influence legislation regarding drug law, and most importantly, treat and offer new ways to help treatment-resistant patients.

[1] Tupper, K. W., Wood, E., Yensen, R., & Johnson, M. W. (2015). Psychedelic medicine: a re-emerging therapeutic paradigm. Canadian Medical Association Journal, doi: 10.1503/cmaj.141124.

[2] Abraham, H. D., Aldridge, A. M., & Gogia, P. (1996). The psychopharmacology of hallucinogens. Neuropsychopharmacology, 14(4), 285-298.

[3] Halpern, J. H., & Pope, H. G. (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and alcohol dependence, 69(2), 109-119.

[Interview] Phil Wolfson deems MDMA, ketamine and psychedelics “not terribly different”

December 6, 2021 / Articles, Interviews, Ketamine, MDMA, Publications / By

Philip E. Wolfson is a psychiatrist and psychotherapist who used MDMA legally in his practice in the 1980’s. A founding member of Stanislav and Christina Grof’s Spiritual Emergence Network and of the Heffter Research Institute, he has held a long-time interest in the use of psychoactive substances as adjuncts to psychotherapy. Currently, he is working on the early stages of a MAPS clinical study on the use of MDMA to relieve anxiety in patients with life-threatening illness.

You were trained as a psychiatrist and therapist, and you worked in those capacities for most of your life. How did you cross over to psychedelic research?

There was no crossover, actually. The research that’s arisen comes out of the illegalisation of MDMA, in this case. I was doing clinical work with MDMA in the 1980’s, with a large group of other therapists, psychiatrists and psychologists, when it was suppressed in 1985 by making it illegal. People either went underground or stopped. But the promise of that research was so great that I stayed attuned to being able to do that. As organisations like MAPS and Heffter began to have mild success with the FDA, and were able to do research on a very small scale, I became involved again. Also, I had lost my oldest son to leukaemia, and I was very involved with people with cancer and life-threatening illnesses and their families. So it really wasn’t a crossover, it was a natural kind of confluence of various interests in my life.

You use another substance, ketamine, in your current practice as a treatment against depression. Has this always been legal? Do you need a licence to use it, or how does this work?

Unlike MDMA, which is a Schedule I drug, like LSD, ketamine is a dissociative anaesthetic, and it’s Schedule III. It’s been in widespread use as an anaesthetic and analgesic. In the 1970’s, the late Salvador Roquet, a Mexican psychiatrist of great consequence, began recognising that in the sub-anaesthetic realm – dosages that were less than what put people to sleep – ketamine caused major psychedelic phenomena. This was also occurring among surgical patients who, when they came out of anaesthesia, often had exit effects that were very perplexing and often disturbing. So this began to be explored and the potential of ketamine as a psychedelic agent became widely known. It’s even been banned in Russia because of street use and is a drug of widespread abuse in China. It has a spectrum of use from low-level, which causes a kind of sedative effect, to what’s called the “k-hole”, where for a period of time, say 45 minutes with a significant dose, people have truly deep and transformative psychedelic experiences.

To add to that, in the late 1990’s, some people at the National Institute of Mental Health (NIMH) began to explore ketamine in even lower dosages, trying to eliminate the psychoactive properties and retain what had been perceived to be an anti-depressant effect in some individuals. They developed what I call the intravenous drip method, in which they use 0.5mg/kg instilled over 40 minutes in a slow drip, so there’s not particularly much of a psychedelic effect. They began to claim, somewhat adventitiously, off another experience that was just by happenstance, that there was an antidepressant effect. Unfortunately, that antidepressant effect is very short-lived and doesn’t persist for most people.

So there were these two tracks, and the NIMH track began to develop a method which enabled off-label use for a different kind of indication, in this case what was called ‘treatment-resistant depression’. A body of literature emerged, which enabled people like myself to say: “Off-label use is not covered by malpractice insurance, if we’re going to do this, we’ll have to have very stringent protocols and informed consent methods, but we can begin to use it as an antidepressant and, more importantly, as a transformative experience.” That’s the kind of work I and quite a few others are doing more and more. Methods remain very variable, and because the anti-depressant effect tends to be short-lived, there are more and more sessions being added on to clinical practice – so, series of sessions over time. It is an evolving practice that needs a lot more information and clarity.

What’s also occurred in the United States is that there are an increasing number of anaesthesiologists involved in providing the intravenous treatment for depression, so it’s not even psychiatrically oriented. I see this as: “I can make some money, I’ll set up a ‘clinic’ and treat some people with low-dose IV for 45 minutes. They can walk out and maybe there’ll be a difference.” So it’s promising in some ways and it’s controversial in others. We don’t know enough yet, either about my methods or about the antidepressant IV methods to say definitively this is a great antidepressant. I don’t think so, I think like all things that are useful in this realm, it has to be embodied within a psychotherapy framework. It’s a different kind of psychotherapy, because people are really not present in an emotive contact way for periods of time until they come out of the influence of the drug.

You were the editor of a recent thematic issue on ketamine of the International Journal of Transpersonal Studies. In one of your articles, you expressed the view that the antidepressant effect of ketamine is correlated with the intensity of its psychedelic effect – or at least, that if you suppress the psychedelic effect, you’ll probably suppress the antidepressant effect as well.

Well that’s the controversy, you’ve put your finger on it. I don’t know if it’s correlated with actual dosage, because at some point you get anaesthesia. But yes, I think if you suppress the psychedelic experience, the antidepressant effect will vanish too. I think that’s really the controversy, and it remains to be shown both ways.

It seems that results with classical psychedelics are more long-lasting, while the effects of ketamine experiences seem to fade over time. Do you think there’s a real difference between ketamine and the so-called ‘classical’ psychedelics?

No, I don’t, and I don’t think it’s true that it fades more with ketamine than with LSD or psilocybin. I think what we see with, for instance, the Johns Hopkins work with psilocybin is that profound – often dosage-related – experiences that are peak or transformative experiences have a more lasting impact on us. Any of us who did LSD way back as a first drug, or MDMA for that matter, as an empathogenic first experience, had very important experiences from it. I don’t think that’s any different for ketamine. People have profound, transformative experiences that last, in terms of impact on soul, impact on imagination, and they discover how vast their minds are. I don’t think any of those substances are terribly different in that sense. I don’t think we can distinguish between them, like one is good and one is bad, or one more powerful than the other.

Ketamine is definitely not a classical psychedelic, though. What would you say are the differences in effects and nature?

Ketamine has a different mechanism of action, but I don’t think its effects are so different from classical psychedelics. You have to lie down, you go into an altered, deep space in which you’re journeying through the cosmos, and personal, psychological, mythic, transpersonal, cultural, philosophical experiences arise, generally unbidden. I think that applies as a taxonomy of experience across the psychedelic board with different amounts of different substances producing somewhat different effects as they have different effects within the brain. Anyway, there are so many hundreds of psychedelics out there, with new ones coming every day, so what’s classical and what’s not? We’re not going back to Mozart here, we’re going back to 1943…

You mentioned that it’s easier to use ketamine because it’s a Schedule III substance, unlike the others that are on Schedule I. What are some of its other advantages or disadvantages, like the fact that it’s short-acting, and most often injected instead of ingested, or others still?

I’m not so sure these differences are critical. The shortness of the peak experience, 35 minutes to an hour, with a trail-off of another hour or so, is not discouraging at all, because time dilation within that framework is so extreme…

What I meant is that the shortness of action is more practical for the therapist, who doesn’t have to spend the whole day.

You spend three to four hours, there’s just no way around it, because people have to recover. It’s not a simple walk to the convenience store. The IV method is convenience store, people don’t go that far, they can walk, they’re not really asleep, they’re always conscious. The IV format is easy, the intramuscular format is not so easy. And if you compare duration of action, DMT is 10 minutes and you’re walking, 5-MeO-DMT is 18 minutes, or 40 minutes, however you slice it, so ketamine is not that short-acting.

Regarding the route of administration, oral use of ketamine requires a lot of material and is unpredictable regarding absorption and timing. The nasal route is easy to use and is the main route for street use. There’s no reason to do medically based work using the intravenous method save for analgesia. For psychiatric work, it makes it very medical, and I think it’s an alienating kind of format. The intramuscular method is safe, the drug is relatively safe, so I don’t think that’s intimidating. And, yes, you have to stay with your people until they are safe and you have helped them to re-integrate.

You devised a study with ketamine in order to examine this NIMH protocol and its claim of antidepressant effects, but you enrolled non-depressive subjects who were experienced with ketamine.

The idea was that a group of experienced users of ketamine – very intelligent, thoughtful people, some of them psychiatrists – could not understand how the NIMH protocol had any meaningful impact on anyone, because the intramuscular use is so much more profound. What we were reading and learning about the NIMH protocol was not. We didn’t have a group of particularly depressed people, we weren’t really measuring depression. We tried to have a set of experiences with the NIMH IV method that would give us some sense of comparison. In fact, knowing people over many years with longitudinal experiences, I’m not clear that ketamine is a great antidepressant, but I’m not clear that any psychedelic is a great antidepressant. The motivation of the study was to see what our own experience might tell us about what was being purported to be this great new breakthrough, which had been touted on Science magazine’s front page. And basically what people found was a very innocuous, not particularly meaningful experience.

We couldn’t really comment on depression, as you pointed out correctly, because the group was not composed of depressed people. So it’s theoretically aimed at what the effect on depression would be. The question is: what are the psychological mechanisms of action of ketamine? If you have just a mild kind of swoon, a kind of light taking yourself out of time as in the intravenous method, you have little highlights of psychedelic, but you don’t have much of an experience, so what does it mean? Why would that be helpful, as a 45-minute experience of being lightly anaesthetised, with a mild change in sensory modalities? Why would that do anything? And I don’t think it does, but there are reports – and I can’t debunk them completely – that say that doing that, people get an antidepressant effect if you do it enough times. Single dosage doesn’t seem to have much impact, it’s very short-lived – minutes, hours, a few people have days. So, it has been evolving into many consecutive IV sessions over weeks’ to months’ time with boosters to keep the effect going – if it occurs. Each time, it is a mild interruption of consciousness.

The larger argument is: why do the psychedelic effects of ketamine have an antidepressant or peak experience effect – when they do? You can look at it through a few aspects. One is of course set and setting. If you do it in a good setting you tend to have a better result than if you don’t. If you interrupt ordinary consciousness sufficiently, and you’re taking a break from the obsessional nature of the things that keep you going with depression, anxiety or confusion, there’s an interruption, and ketamine is certainly a very significant interruption of consciousness at the dosages that we’re using. This also goes towards electro-convulsive therapy, and the traditional therapies of interrupting consciousness. If you add to that the kind of brain scramble of a psychedelic experience which ketamine and others provide, this new mind-manifestation kind of experience, what we mean really by ‘psychedelic’, that people are having new experiences, that brain and mind are reorganising, then I think you have the capacity for both a change in mood and a change in consciousness. These two particular aspects, interruption of consciousness and new formation of consciousness, or reformation of ordinary consciousness, bring the possibility for real change.

It doesn’t happen all the time, though, people are very tough. Many people have done hundreds of acid trips, and seem pretty much the same. Our character re-exerts itself, so I think that’s one of the great riddles: why do we stay the same? I don’t have a clear answer, but we have definite strong pathways laid down in mind and brain that keep us humming in the same direction. Psychoactive treatment, I hope, is disruptive of that, in a good way. That’s why I think a therapy setting is important, because the disruption also has to be integrated, it has to be put back into a life stream, into a context, a community, integrated in the values that people hold, which are critical to any change. If you do a trip and all you see are lights and colours, and you come back and say, “Those were beautiful lights and colours, I really like that, I’ll do more lights and colours,” it’s not quite the same as saying, “What’s my attitude towards violence, or towards women, or racism, or what’s my being in the world, with nature, how do I perform and make my own character better?” That’s why I think a therapy that’s addressed to that – and not all therapies do that – is an imperative if we want to create a world of sharing, love and connection.

You’ve started conducting this new study with MDMA for people with anxiety related to life-threatening illness. You seem to consider MDMA as a genuine psychedelic as well. What differences and similarities would you point out with ‘classical’ ones?

I think MDMA is classical, it arose in the 1970’s. It all depends on how you define classical. The only real classical is nitrous oxide, right? It’s from the 1790’s, the second would be morphine, then mescaline with Arthur Heffter in 1897, etc.

Yes, but many people label it an empathogen or entactogen, and won’t consider it a psychedelic. What’s your opinion on that?

Well, it arose from Alexander Shulgin’s research, who was rediscovering phenethylamines, mescaline analogues. Before we ever coined the term ‘empathogen’, it had this quality of a different kind of experiential space that was very related to other psychedelics, particularly in those days LSD and mescaline, peyote and mushrooms. But it’s not psychedelic in the sense of ‘hallucinogenic’. So the differentiation is around ‘hallucinogenicism’, that is the ability to create mind manifestations that are hallucinogenic. The term ‘empathogenic’, which I prefer over the others because I think it’s accurate, is not unique to MDMA either. We call a bunch of other substances, even LSD, empathogenic, depending on dose. Otherwise, 2C-B for instance is considered to be an empathogen with mild hallucinatory properties.

The beauty of MDMA in the work we were doing from the late 1970’s on until 1985 was that it was fabulously helpful in making people feel an ability to reach out to others and themselves in compassionate ways, and to handle what had been otherwise fearsome negative experiences, so that there was a warming that you could feel with it, and that warming came to be called empathy for good reason. But empathy is more than a warming, it’s the ability to put yourself in others people’s shoes, or in your own shoes but in a better way. So it became very potent as a psychotherapeutic experience. It revolutionised therapy – although LSD therapy had been doing it as well – in that you had to be with people for three to six hours. No therapy of the psychoanalytic or psychotherapeutic sort, with their 45- to 50-minute hours, was doing that much time with people. So the contact point was huge, and the knowing of the person or persons you were sitting with was immensely different. And because it enabled the re-examination, the feeling examination of oneself and one’s relationships, its potency for a quicker, more breakthrough, less defended kind of therapy was manifested.

Compared to previous end-of-life studies with LSD and psilocybin, is your protocol roughly the same, or did you include significant differences?

We’re not doing end-of-life, it’s more similar to the psilocybin protocol done at Johns Hopkins, in the sense that we have excluded terminal illness. We’re placebo-controlled, we’re doing at least three MDMA sessions, and up to five overnight sessions. We’re doing them in my home, and I’m there with my co-therapist and partner Julane Andries. These are 6- to 8-hour sessions with 24 hours of contact that are very taxing. In fact the intensity of the therapy is so strong that we’re with people 17 or more times, including those 3 or 5 sessions. So it’s a very exacting protocol, and we couldn’t bring in people who might be actually facing death or major events in the time period of the study, because that would distort the effects of MDMA and the therapy. So we created a boundary, as Hopkins did, which was that there would be at least 9 months of life expectancy. In fact, we’re having people coming to the study who are either in maintenance therapy for cancer or other illnesses, or they’re free of cancer as far as they know, but facing the possibility of recurrence, relapse and potential death. We needed to have enough space and time so that we could do the work and the measurements, which couldn’t have happened if this was truly and end-of-life study with terminally ill people.

The protocol goes as follows. First there are two sessions, either both with MDMA or both with placebo, in a randomised double-blind setup. We just had an amazing surprise there by the way, where Julane and I thought the person was on MDMA, when in fact they were on placebo. I was absolutely certain, but it was actually the effects of set and setting and therapy, and they had a marvellous experience. They had less certainty about it. So that was a great humiliation of my ego there, and I loved that it meant I could be wrong about something and still have the experience of a very positive effect. After the two overnight sessions, the study moves to a primary endpoint where we compare MDMA and placebo over those 2 sessions. If people got the placebo, they can go on voluntarily to 3 more sessions with MDMA, so they go on to a total of 5 sessions. Those who received the active dose in the first two sessions end the process with a third MDMA session. We have a secondary endpoint where we examine the impact of all 3 MDMA sessions. Finally, we have a 6-month follow-up and a 12-month follow-up. Right now, we’ve completed one subject, we have six more going, and there will be a total of 18 subjects. The whole process will take us a year and a half, and the first results should be out in 2017.

You’ve had personal experience with the use of MDMA in situations of distress, both as a therapist and as a father faced with the life-threatening illness of his son. Did this play a role in the choice of substance and/or subject population?

No, I don’t think it was an influence. My son, to be clear, didn’t use the substance, it was embedded in a framework where my wife and I used MDMA in the legal period with our kids being around. My son had leukaemia, which was a very difficult and traumatizing experience for all of us and then we lost him after nearly 4 years.[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”][1] MDMA was beneficial to us on that personal level, and MDMA was beneficial to many people including myself in the couples and relationship therapy framework. No, I don’t think it influenced the choice of drug. I just think MDMA is a fabulous psychotherapy tool, and the fact was that MAPS and Rick Doblin had made great strides toward getting FDA research on MDMA going. So I was very pleased to have the opportunity to work with it that way. As for the field of research with life-threatening illness, I didn’t entirely choose it. Rick Doblin and MAPS had received a bequest that was aimed at that. The interest of the person who had died was towards giving money to explore MDMA with life-threatening illness. So there was an opportunity, Rick came to me because of my son and my history as a doctor, my interest in MDMA and our connection over many years. He honoured me by asking if I wanted to do this study, and I sort of leapt at it and said, “Great, let’s go!”

[1] Phil Wolfson wrote a book about his family’s ordeal: Noe – A Father-Son Song of Love, Life, Illness and Death, North Atlantic Books, 2011.

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Breaking Convention 2015: Looking back (and forward)

December 6, 2021 / Articles, Events, History, Public Lectures, Publications / By

BC_report_2Psychedelic researchers gathered from all over the world to present their findings at the third biannual Breaking Convention conference (BC). The conference took place at Greenwich College in London between 10 and 12 July and hosted 140 presenters from about 40 countries as well as performers, artists and musicians. Over 800 people attended the event, which included renowned presenters such as professors David E. Nichols, David J. Nutt and Roland Griffiths, along with a great variety of academics from different disciplines.

According to Dr. Ben Sessa, one of the conference’s organisers, the conference was a success: “We have had a lot of great feedback. BC is a very ‘home grown’ affair, with almost a third of delegates participating in one way or another. People feel a great deal of personal ownership over the conference, which means the atmosphere is great and a lot of important networking gets done.” Sessa was one of the co-founders of BC in 2011, and explains how the conference has built momentum since then: “We set up BC as a platform to showcase psychedelic research and culture. The conference has grown tremendously and we hope it will continue to expand and inspire young people and seasoned enthusiasts to propagate this important subject.”

One of the participants was Michael Kugel, an undergraduate medical science student from Sydney, Australia. He travelled 17.000 kilometres to meet world leading researchers in current medical cannabis and psychedelic research. He thinks his trip was worthwhile and shows that Sessa´s hopes are not in vain. “I’ve met a lot of great people here”, says Kugel. “I met Allan Badiner, author of Zig Zag Zen, who introduced me to MAPS founder Rick Doblin, who in turn told me about a psychiatrist who is trying to get approval in Australia to study MDMA for PTSD in war veterans. At lunch I bumped into Lumír Hanuš, who was part of the team that discovered anandamide [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”][an endogenous cannabinoid, ed.], and who currently works with Raphael Mechoulam. I offered him my (limited) lab skills – we’ll see where that leads. I´m feeling really good about it all so far.”

For Tehseen Noorani, a researcher who has participated in a psilocybin studie at Johns Hopkins along with Roland Griffiths and Matthew Johnson, coming to BC was a no-brainer: “I do research on psychedelics and these conferences are rare. They are also big, so it totally makes sense to come and present work and find out what else is going on. When you´re in this space, you realise how much is going on – there are so many small pockets of activity all over the world.”

Noorani thinks it’s important to undertake efforts to further convince funders that psychedelics are a topic worthy of research. “For me there are a lot of sciences,” he said. “I work with pharmacologists and the steps forward for clinical trials seem to be pretty straightforward. As there´s a growing acceptance of the impressive outcomes of strictly scientific research, what we really need now is money.” He also underlined the importance of taking social scientific research around psychedelics more seriously: “My background is in anthropology, and I would say anthropological work needs to be taken more seriously. Firstly, research needs to connect the important anthropological and political questions of today. Secondly, ethnographic research needs to be recognised as serious research by so-called harder sciences, and by the public, because to be interested in psychedelics is to be interested in pretty profound stuff.”

Levente Móró, a consciousness researcher from Finland currently based in Hungary, also found what he came looking for: “Along with the interlaced biennial conference by the OPEN Foundation, BC is the most important European meeting of the international psychedelic science field. I wanted to get updated about the status of current research, to meet old and new fellow researchers, and to put forward my own ideas and receive feedback. The conference provided abundant amounts of knowledge, from all the various fields related to psychedelics. It is nice to receive fresh input and viewpoints, also from outside my own fields of study. Moreover, it has been extremely nice to meet more people from Finland, as a result of the recently organised psychedelic science activism.” A group of academics in Finland, who aim to promote practical research and evidence-based information on psychedelics, organized their first small psychedelic seminar last April, with presentations from Teri Krebs, Murtaza Majeed and Helle Kaasik, among others.

Móró’s own presentation at BC was based on a bioethical analysis of the 1961 Single Convention on Narcotic Drugs he produced with his colleague Imre Bárd, who wasn’t present. He focused on representations of ‘evil’ and demonstrated how the UN drug laws used a language of religious immorality to justify drug prohibition. His presentation, although based on a convention that was signed over half a century ago, found resonance in current legislative practices. One of the hot topics mentioned during many of the BC presentations was the new Psychoactive Substances Bill (2015), proposed by the British government just weeks before the conference. The new bill would increase the regulation of most psychoactive substances (not including alcohol and tobacco) and further complicate psychedelic research. An open letter was published on the conference website, addressed to the British Prime Minister, in which the undersigned urge for the content of the Bill to be reconsidered. It was signed by over 40 professionals, including academics, former and current members of Parliament and police officials.

This more politically active role of psychedelic researchers was welcomed by Levente Móró: “It was nice to see that psychedelic researchers have been getting involved more and more with drug policy reform issues.” Despite the possible tightening of regulatory practices in the UK, Ben Sessa seemed optimistic about the future of psychedelic research. “Psychedelic research requires a major Public Relations drive. Most researchers believe that psychedelic drugs are useful, safe and efficacious tools for medicine, growth and development. But sadly, for the majority of the general public, high levels of stigma and misinformation remain attached to these fascinating substances. This means we need to detach ourselves, to some extent, from the “hippie” genre and demonstrate that ‘normal’, everyday people can use psychedelics safely and with personal and communal benefits. One way of doing this is to increase the exposure of psychedelic medicine to people everywhere through the media. This is partly why I wrote my novel ‘To Fathom Hell Or Soar Angelic’, which was launched at BC15. In the meantime, my clinical colleagues and I continue to carry out robust scientific studies to determine the safety and efficacy of psychedelic therapy.”

One way to relieve the stigma could be for researchers to openly discuss their own experiences. But could this harm their credibility as scientists? Noorani: “As a researcher I would say there´s a real dilemma around admitting to having (not) taken psychedelics in terms of how it legitimises or delegitimises the research you do.” Móró believes that scientific credibility should not rest on the researcher´s person: “Researchers might get insights from their own experiences, or become more motivated to investigate phenomena they find personally fascinating and meaningful. Besides, scientific credibility should not depend on a researcher’s personal background. It should be objectively assessable and independent of the researcher’s non-scientific traits or parameters.”

While Sessa openly discussed his own experiences, he also recognises how legal restrictions might affect the extent to which professionals publicly speak about their use of psychedelics: “I am fortunate to have participated in a number of legal psychedelic research studies in the last 6 years, so I can say, on the record, that I have taken ketamine, LSD and psilocybin in those studies.” Sessa supports the idea that ‘coming out’ about safe and beneficial experiences could be a good way to forward the emancipation of these substances: “This method worked well for driving the normalisation of homosexuality in recent decades. However, I also understand professionals – especially doctors – who feel reluctant to do this. The possession of illegal drugs is still penalised in most countries.”

Next year, the special session of the UN General Assembly Special Session on Drugs (UNGASS) will, among other things, give directions for the future of psychedelic research, and the outcomes will probably be extensively presented, discussed and debated at the next BC in 2017.

This report is based on on-site recorded interviews and post-conference email interviews.

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Symposium October 30th: Comeback of psychedelic drugs in science and medicine

December 6, 2021 / Articles, Events, Public Lectures, Publications / By

11227635_1628720620748797_8237747453050699295_nAfter 50 years of prohibition, psychedelic drugs are making a comeback in science and medicine. On the 30th of October, four scientists from the pioneering labs of David Nutt and Tomas Palenicek will present their cutting edge work from the forefront of psychedelic research. Cognito, in collaboration with Czech Psychedelic Society and the OPEN Foundation, is pleased to invite you to this extraordinary event.

Date: October 30th, 16:00-20:00
Location: Oudemanhuispoort, University of Amsterdam

WE’RE SORRY TO ANNOUNCE THAT THE EVENT IS SOLD OUT.

Four speakers will present their experiments on the influence that certain psychedelic drugs such as psilocybin (found in magic mushrooms), and Lysergic Acid Diethylamide (LSD) have on ordinary consciousness. The use of neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG), has recently shed light on the neurocognitive mechanisms underlying these altered states of consciousness. A total of four speakers from Prague and London will present and discuss these exciting new findings in the symposium.

Programme:

16:00 – 16:20 doors open
16:20 – 16:30 short intro

16:30-17:10
Speaker: Filip Tyls, MD
Title: Psychedelic research in the Czech Republic – comeback after 50 years
Abstract: Filip Tyls is a psychiatrist and PhD Researcher at the National Institute of Mental Health in Prague. His main research interest is the neurobiology of psychedelics, addiction and serious mental disorders. Filip will kick off the symposium with an introductory talk entitled: “Psychedelic research in the Czech Republic – comeback after 50 years”. He will provide a short historical overview of psychedelic research and discoveries in the Czech Republic. In addition, he will present current ongoing projects and prospects for the future.

17:10-17:50
Speaker: Tomas Palenicek, MD, PhD
Title: Psychedelics as unique tools for understanding psychosis.
Abstract: Tomas Palenicek is a researcher and psychiatrist at the National Institute of Mental Health in Prague. Since 2001, he has been researching the neurobiology of various psychopathologies in a clinical neurobiology setting, using psychedelic drugs. Tomas’s research team was the first to be granted approval to conduct research on psychedelics with human subjects in the Czech Republic after 50 years. His talk, entitled “Psychedelics as unique tools for understanding psychosis”, will argue for the relevance of modern research with psychedelics, and provide examples of how these substances can be used in clinical settings.

17:50-18:10 Coffee/tea break

18:10-18:50
Speaker: Mendel Kaelen, MSc
Title: t.b.a
Abstract: Mendel Kaelen is a PhD candidate at Imperial College London. His research focusses on the effects of psychedelics on music-evoked emotion, and on the role of music in psychedelic-assisted psychotherapy. He recently published a paper on this topic in the scientific journal “Psychopharmacology”, and in his talk he will continue this discussion by sharing insights from his research at Imperial College London. This will include neuroimaging studies with LSD and music, as well as a recent study to the role of music in psychedelic-assisted therapy for severe depression.

18:50-19:30
Speaker: Robin Carhart-Harris, PhD
Title: t.b.a.
Abstract: Robin Carhart-Harris is a post-doctoral researcher at the centre for Neuropsychopharmacology at the Imperial College London. Robin is one of the leading investigators of the field of psychedelic science. By using neuroimaging techniques such as fMRI and MEG, Robin hopes to reveal the brain mechanisms underlying altered states of consciousness caused by the use of psychedelic substances. Moreover, he is an author of the Entropic Brain theory, which provides a connection between modern neurobiology, psychoanalysis and theoretical physics.

19:30 Room for questions and discussion

[Interview] Felix Hasler: “What’s missing is a holistic view on the psyche”

December 6, 2021 / Articles, Interviews, Publications, Spirituality / By

Felix_Hasler_Portrait_by_Oscar_Lebeck_(G&G)-cropAs a psychopharmacologist, Felix Hasler has studied the pharmacology of psilocybin over a decade together with Franz Vollenweider at the University of Zürich. A short time later he published his book “Neuromythology”, in which he argues against the current hype within the field of neuroscience and for a more moderate and humble scientific practice. Felix is also a member of the neuroculturelab, a multimedia project aiming to raise awareness of the modern view of the self that is suggested by brain researchers and is the subject of controversial discussion among philosophers. We met in Berlin, where he is currently a guest researcher at the Berlin School of Mind and Brain (Humboldt University), to talk about current tendencies within the neurosciences, mental disorders and the medical application of psychedelics.

Mental disorders are on the rise and research labs around the world are trying to improve pharmacological intervention, ranging from finding biomarkers for schizophrenia to genetic screening for depression. In your book “Neuromythology”, you express your doubts towards the successfulness of such biopsychiatric experiments. Can you shortly explain why?

The big buzzword we talk about here is the one of “personalised medicine”. It creates the impression that mental disorders could soon be treated on an individual basis. Treated pharmacologically, I should add, since psychoanalysis of course is traditionally a highly individualised way of dealing with mental problems. In the biomedical context of mental disorders, I think that “personalised medicine” is a big illusion. We still have no clue how depression emerges from the brain – if it does in the first place. Even in somatic medicine, personalised medicine works in only 2 cases to date. First, there is Herceptin, a chemostatic against certain types of breast cancer. It is known that tumour cells produce different levels of the protein onto which the drug binds. The higher this protein expression, the higher the efficacy of the drug. Secondly, some drugs can be prescribed “personally” when it is known whether the patient is a slow or fast metabolizer of the substance being prescribed. Thus overdosing can be avoided. But especially in psychiatry, the only remedies available today act highly unspecifically, e.g. antidepressants.

Is it the research methods that have to be improved in order to one day establish individualised treatment for mental disorders, or is it simply impossible to completely understand the aetiology of illnesses of such a complex system as the human brain?

If you look back in the history of psychiatry, there has always been discrimination between psychiatric and neurological disorders. Ones that could be treated with classic medical interventions (drugs, surgery, substitution, etc.) and ones that could not. Today, we have a more complex situation where this distinction is almost given up. At least in the academic discourse, everything is conflated in the umbrella term “neuropsychiatric disorders”. There certainly are examples of mental symptoms that can be explained on a neurological basis like Dementia with psychotic episodes or Chorea Huntington. However, with other affections such as depression or schizophrenia, the face of affairs seems to differ a whole lot. This leads me to believe that there won’t be any specific and truly successful drug treatments for mental disorders in the future. There is no such thing as a “depressive brain”. Therefore we don’t even know the target configuration of a “non-depressive brain” that we could reinstall by some kind of biomedical treatment. One reason for this is the immense physiological variability in human brains. The expression of, let’s say, a specific serotonin transporter that is discussed to be involved in depression fluctuates within several hundred per cent in large enough study populations. Ergo, it is very difficult to extract a general hypothesis on healthy or diseased brain physiology regarding depression. Focussing on single neurotransmitter systems such as serotonin and changing their functionality (eg. by SSRIs) has not shown to be very effective. Neurons don’t get depressed, only humans do. Mental disorders, in my view, are disorders of consciousness and therefore have to be treated on a much more holistic level, taking the whole human being into account. I’m aware that many biological psychiatrists say the same thing. But when you then look at the current clinical practice, this seems little more than lip service.

When you say that the prescription drugs against depression and schizophrenia don’t really have medical benefit for the patients, are the definitions and medical treatments of these disorders just a scam in order to sell more and more pharmaceuticals?

There are of course criteria to classify mental disorders in order to inform medical treatments. The process of these groupings, however, is not based on scientific grounds. The whole mental diagnostics are in fact decisions by members of the American Psychiatric Association (APA) who compile their results in the DSM, the Diagnostic and Statistical Manual for Mental Disorders. It is a pretty simple system of expert consensus that defines which psychological state is deemed a mental disorder and which one is not. From these rather arbitrary definitions arise fashionable complaints for people that objectively have no pathological significance. Someone who is by nature an introvert may thus be diagnosed with social anxiety and treated with SSRIs. That’s a classic case. On the other hand, some disorders become very rare in clinical practice – such as catatonic schizophrenia – or disappear entirely from the diagnostic manual, such as hysteria, which was very common in Sigmund Freud’s times. I would not go so far as to state that depression is another myth put out by “big pharma”, however it is interesting that more and more people are diagnosed with depression without clear evidence that there are indeed more depressed patients than decades ago…

…because naturally occurring melancholic phases that every one of us experiences from time to time are being pathologized?

Precisely! The pharmaceutical companies have an intrinsic interest in increasing the number of psychiatric patients – at least on paper – in order to sell their products. With the previously mentioned human-made definitions of mental disorders this is easily achievable. Their tool is the so-called “disease awareness campaign”. This happens in accordance with patient organisations and sponsored of course by the respective pharmaceutical industries themselves. The result of such a campaign is that a person hears that if they experience symptom abc, they should go see a doctor and check for disease xyz. They then become a patient that they actually aren’t and have to take medications that they do not need.

As well as I can retrace your line of argumentation, shouldn’t you as a neuropsychopharmacologist be in favour of such pharmaceutical developments? In 2006, at a symposium in honour of Albert Hofmann’s 100th birthday, you were still convinced that a more detailed analysis of the serotonergic neurotransmitter system would automatically lead to a better understanding of some mental disorders.

10 years ago I was indeed still convinced that there is something like a “neurochemical self”. By that I mean that conscious experiences and mental disorders can be explained in a reductionist way by investigating the neurobiological foundations of these mental states in a scientific way. Hallucinogens such as psilocybin are in that sense a perfect tool, as they pharmacologically act very specifically on certain serotonergic receptors and psychologically result in a very profound alteration of consciousness. I am still very much in favour of research into psychedelics because I believe that they possess a big potential for treatment in psychiatric institutions. However, I’m strongly convinced that neither the psychedelic experience nor mental disorders can be explained by mere alterations in brain chemistry. What’s missing is a holistic view on the psyche taking into consideration both the isolated brain and the whole person as a social and political being.

With what skills would you equip a future researcher who wishes to study the brain in the context of psychedelics and mental disorders so that they can pursue that goal of scientific holism?

I believe modesty is a rare characteristic that I wish to be cultivated more amongst young scientists. Especially in medical aspects of research there exists a tremendous misinterpretation in the mind of students thinking that science would always result in axiomatic theories that last forever. This is not the case at all! Everyone should take a class in the history of science to get an idea of which aspects of nature actually can be studied and which can’t. This is also important to get a feeling for the philosophical question of what can be known at all and to which degree study results may be interpreted in order for them to still be validated. An example of this are the EEG experiments performed in the 1920’s. Scientists were unequivocally clear about their claim that these visualised brain waves are the biological foundation to explain the phenomenon of consciousness. Or look at the study of phrenology in the 19th century. Advocates of this theory were convinced that they could identify criminals by measuring the shape of people’s skulls. Nowadays neuroscientists look for biological markers in the brain and in the genes that might predict criminal behaviour. Critics of this “predictive neuroscience” say that this is nothing but an updated form of phrenology. A critical attitude towards scientific claims is very important, especially in the neurosciences.

You have worked within this field yourself for 10 years at the ETH Zürich in the lab together with one of the pioneers in the second wave of psychedelic research, Franz Vollenweider. What was your motivation to do so?

On the one hand it was the fundamental research within the neuroscientific field that I found very interesting. On the other hand it was the scientific examination of human consciousness. Substances like psilocybin are tailor-made for that endeavour in that they display an ideal interface between biology and the soul, psyche or however you may want to call the mental aspect of the human experience. There is also the field of “experimental psychopathology” with psychedelics, but I’m sceptical about the epistemic and practical usefulness of the “model psychosis” paradigm. I am a strong supporter of investigating the medical properties of psychedelics, however I wonder if it is possible to extract objective scientific insights with hallucinogens given the subjective nature of a psychedelic experience. In Zürich I learned how extremely difficult it is to explain states of consciousness that emerge from substances like psilocybin by scientific means.

Do you think that this is even necessary? In the case of mind-altering drgalateaugs, isn’t it the subjective experience of the experience itself that initiates the healing process in a patient?

It depends on which substance we are talking about. With the application of MDMA I think the treatment should always have a depth psychological approach in order to reach the maximum effect – take the MDMA-assisted psychotherapy against posttraumatic stress disorder as an example. With ketamine against depression I am not sure whether a “full-blown” experience is necessary to evoke its medicinal properties. The answer to this question depends to a high degree on who you ask. A curandero in Peru who works with ayahuasca won’t care a lot about the pharmacological principle of DMT. It’s “mother Ayahuasca” who treats the soul of the patients. I like that idea because it fits into the holistic principle of healing I talked about. A bio-psychiatrist in the Western world, on the other hand, would probably be very much interested in the biochemical pathways that such a substance will create in order to synthesise analogues that can be sold as pharmaceuticals.

What is your opinion on psychedelic science in the future?

Everyone who has undergone a psychedelic experience first-hand would agree that substances like psilocybin and LSD are very potent and can be highly effective tools. Shortcuts to the depth of your soul – and possibly to the roots of your mental problems. But psychedelics are very sharp knives with which you can also cause a lot of harm if not handled correctly. With every experience, you start into an uncertain journey. That journey might turn into something beautiful, meaningful, eye-opening and even life-transforming, but you may also find yourself in the pit of a horror trip. Both the future of scientific research and the acceptance of psychedelic treatments in society will depend on how much the uncertainty in the outcome of a psychedelic experience can be controlled and steered. But again, there is so much variety in the psychedelic experience. And in biomedical research there is always the problem of the impact of a scientific clinical setting on the experience. In PET studies with psilocybin we did in Zürich, we saw that study subjects who managed to turn to their inner world had very positive experiences, whereas others who focussed on the outside world had quite a hard time given the anxiogenic sterile high-tech environment of a hospital PET centre. That was about 50:50. But how can you predict beforehand who will have what type of experience?

What is your advice to someone who would also want to engage in psychedelic science?

Unfortunately, I don’t think that there is a general plan or even an academic curriculum that you can follow. It depends a great deal on the political circumstances. Switzerland for instance is quite an ideal country to do psychedelic research, because politicians and healthcare officials there are not ideologists, but pragmatic bureaucrats. You can do research with almost any substance if your experimental design is sound, the study planned seriously and conducted in a strictly scientific way. Of course, ethics committees need to agree on your research plan and attest that your subjects won’t be at risk to be harmed. In that case, the Swiss government will not only tolerate your work but will also actively support it. In the US, of course, Rick Doblin from MAPS, a “man on a mission” advocating the medical use of psychedelics since the 1990s would be someone to talk to about research opportunities. One reason why research with LSD and other psychedelics might be easier in the future is because hallucinogen research “2.0” got completely depoliticised and doesn’t follow any agenda of societal revolution anymore. Contemporary “neuropsychedelia” – a term coined by the anthropologist Nicolas Langlitz – has absolutely nothing to do with a political propaganda à la Timothy Leary. So there is a chance that psychedelic research will even enter mainstream biomedical research, at least to a certain degree. In the case of ketamine, this is already taking place.

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

The central unanswered question still is – and will probably be for a very long time – how consciousness emerges from brain processes. To have a brain seems a necessary requirement for consciousness. But is it sufficient to fully explain the phenomenon? What western science seems to have long agreed upon, namely that “mind is what the brain does”, seems not so evident to me. Maybe consciousness is a fundamental characteristic of the universe, just like a negative charge is a fundamental characteristic of an electron, or gravity is a fundamental physical property of mass. And there is an even more fundamental question: Why is it that we are not mere stimulus-reaction-automata, but that we have conscious experiences so that we can rationally and emotionally navigate in a personal, subjective world? There are dozens of theories out there that aim to answer these questions, some very scientifically oriented, some less. However I have not encountered a single one that is really convincing or even practically verifiable. Personally I have the admittedly unscientific intuition that psychedelics might be key to the answer.

Symposium Utrecht University: Psychedelics – Novel Applications for Depression

December 6, 2021 / Articles, Events, Public Lectures, Publications / By

Unitassymposium

Psychedelics – Novel Applications for Depression

An evening symposium dedicated to recent research into the potential anti-depressant effects and mechanisms of action of psychedelic drugs. Organized in collaboration with U.P.S.V. “Unitas Pharmaceuticorum”.

There’s a recognized need among therapists for more effective interventions for depression. The currently available psychopharmaceutical medications don’t work for everyone. What do we know about the effectiveness of psychedelics? To discuss these topics, we invited three young researchers, from three countries and three related disciplines. All presentations will be in English.

  • Tobias Buchborn is a German neuropsychologist, doing research at the Otto van Guericke University in Magdeburg. He studied the antidepressant potential of LSD in animals and will present his findings and implications for the clinical practice.
  • Mendel Kaelen is a Dutch neuroscientist working at Imperial College London. His talk will cover neuroimaging studies concerning the brain mechanisms of psychedelics and music, and their role in psychedelic-assisted therapy for treatment-resistant depression. You can read about his most recent publication here.
  • Tharcila Chaves is a Brazilian pharmacist, who is currently studying the effects of orally administered ketamine for therapy resistant severely depressed patients at the Medical Centre of the University of Groningen (UMCG).

There will be time for a plenary discussion and Q&A with the researchers afterwards. Please be on time!

Date: September 15th, 2015
Time: 19:00 – 22:00
Location: Marinus Ruppertgebouw (blue lecture hall), Leuvenlaan 21, Utrecht.
Tickets: €2,- for members Unitas Pharmaceuticorum / €7,50 for non-members. Sold on location.
Reserve your ticket(s) by sending an email to assessor1@upsv.nl (Unitas Pharmaceuticorum)

Also see the Facebook event page for updates and more information.

Does LSD enhance the emotional response to music?

February 7, 2022 / Articles, LSD, Research / By

Aside from its hallucinogenic properties, LSD is known to have noticeable effects on emotion. This is one of the reasons why psychedelics were used in psychotherapy in the 1950s and 60s, hypothesizing that they facilitate emotional release and insight  [1][2]. Similarly, music can evoke emotion and was also a component in psychedelic-assisted psychotherapy, for aiding emotional arousal and release, and in promoting the occurrence of peak or spiritual-type experiences [3][4]. Working at Imperial College, London, neuroscientist and OPEN board member Mendel Kaelen and colleagues conducted a study [5] aiming to explore the significance of music in psychedelic-assisted psychotherapy. Using a placebo-controlled setup, the study sought to test the hypothesis that the emotional response to music is enhanced on LSD. The research team also investigated the role of music in occasioning peak or spiritual-type experiences.

Ten participants attended two study days. During one such day, they received a placebo (10ml saline), while on the other day they were given between 40 and 80 μg of LSD, with roughly a week in between. The design was single-blind, which means participants were blind to which condition they were in, but researchers were not. Participants listened to a playlist of five different (mostly neo-classical and ambient) instrumental tracks on each of the two study days, with the order of the playlist counterbalanced across participants. In order to assess the emotional response to the music, participants were asked how emotionally affected they were by the music, which served as the primary outcome. Furthermore, the Geneva Emotional Music Scale (GEMS-9) was used to investigate the specific factors of the participants’ emotional experiences, consisting of nine subcategories of emotion (wonder, transcendence, power, tenderness, nostalgia, peacefulness, joyful activation, and tension). The results showed that the mean scores for the emotional response to music were significantly higher for the LSD condition than for the placebo. Additionally, all nine factors on the GEMS-9 scored higher in the LSD condition than in the placebo, with significant increases for the items “wonder”, “transcendence”, “power” and “tenderness”. Correlational analyses showed a significant positive relationship between ratings of intensity of drug effects and emotional arousal to music.

The finding that LSD enhances the emotional response to music supports the popular assumption that music has more significance under the influence of psychedelic drugs. Emotions of transcendence and wonder are traditionally thought of as core constituents of peak and spiritual experiences [6][7]. This led the authors to infer that the combination of LSD and music may increase the likelihood of having spiritual-type or peak experiences. Moreover, these experiences have been shown to correlate with sustained improvements in well-being and life satisfaction [8] and also with increases in the personality trait of openness [9], which supports the view that music is an important element in psychedelic-assisted therapy.

Due to this being a pilot study, it does come with its limitations. Small sample size and musical genre selection mean that results cannot be generalised to a larger population. Also, participants could have guessed the purpose of the study, meaning the results could reflect their own or the researchers’ expectations. Additionally, results could be attributed to the effect of LSD alone, rather than the specific effect of music in combination with the drug.

When asked about the implications of his study for future research, Mr. Kaelen told us these are just humble first steps in helping build an evidence-based approach to psychedelic therapy. “It’s important to start a discussion on the role of music and the importance of the setting in general within psychedelic therapy,” Kaelen said. “Due to the study’s limitations, future studies have to come up with different designs and more detailed research questions.” Kaelen also mentioned research already underway at Imperial College, including brain imaging studies with FMRI and MEG, which aim to investigate which brain mechanisms are involved. He also emphasised the importance of translating elements into clinical work. “A clinical trial, now in progress at Imperial, uses psilocybin for treatment-resistant depression. Part of this study looks at the role of music, which will hopefully further our understanding of how music and psychedelic therapy work together.”

[1] Busch AK, Johnson WC (1950) L.S.D. 25 as an aid in psychotherapy; preliminary report of a new drug. Diseases of the nervous system 11: 241-243

[2] Leuner HC (1983) Psycholytic therapy: Hallucinogenics as an aid in psychodynamically oriented psychotherapy In Psychedelic Reflections, ed. Grinspoon L & Bakalar JB, pp. 177-192: Human Science Press

[3] Bonny HL, Pahnke WN (1972) The use of music in psychedelic (LSD) psychotherapy. Journal of music therapy: 64-87

[4] Grof S (1980) LSD Psychotherapy. Hunter House Publishers, US.

[5] Kaelen et al. (2015) LSD enhances the emotional response to music . Psychopharmacology [Abstract]

[6] Maslow AH (1993) The Farther Reaches of Human Nature. Arkana

[7] Richards WA (2009) The rebirth of research with entheogens: lessons from the past and hypotheses for the future. The Journal of Transpersonal Psychology Vol. 41: 139-150

[8] Griffiths RR, Richards W, Johnson MW, McCann U, Jesse R (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of psychopharmacology 22: 621-632

[9] MacLean KA, Johnson MW, Griffiths RR (2011) Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of psychopharmacology 25: 1453-1461

[Interview] Michael Bogenschutz likens psilocybin treatment to ‘reverse PTSD’

February 7, 2022 / Articles, Interviews, Mushrooms / Psilocybin, Research / By

Addiction psychologist Michael P. Bogenschutz currently works at the Department of Psychiatry at NYU. Prior to New York, he worked at the Department of Psychiatry and Behavioral Sciences, University of New Mexico.

Much of Bogenschutz’s work has involved searching for new applications of existing treatments for addictions. The OPEN Foundation talked to him to learn more about his research on psilocybin-assisted treatment for alcohol dependence, the first trial of its kind.

Could you briefly describe your career, and what led you to pursue psychedelic research?

My career has focused on clinical treatment and, particularly in the last 10-15 years, clinical research on treating addictions. I have always been deeply interested in how people change and how we can facilitate change in problematic behaviours.

Working with patients, you’ll find people who will tell you they came to a point where they just quit suddenly, while some gradually become abstinent or the problem diminished over time, and others have relapse episodes for years, never improve, or get worse. There is a very real and not uncommon phenomenon of sudden and categorical change in behaviour, which is not unique to addiction. I find that interesting scientifically, psychologically and clinically. Why does this happen to some people and not to others?

I really became interested in research with psychedelics shortly after joining the faculty at the University of New Mexico (UNM) in 1994. At that time, Rick Strassman was doing work with the intravenous administration of DMT. Dr. Strassman left UNM not long afterwards and as I was a junior faculty member, it didn’t seem realistic to pursue my own research in that area. I didn’t think much about it again until I saw Roland Griffiths’ 2006 paper on the effects of psilocybin on healthy volunteers.

I was immensely impressed with both the findings and the fact that it was possible to do these kinds of studies. In that paper, the authors describe the acute effects of psilocybin in volunteers and the relatively high frequency of mystical types of experiences. More importantly, from a clinical perspective, there was a report of the persisting change in attitudes, emotional states and relationships. The follow-up paper two years later documented the persistence of these effects on the basis of a single experience with relatively high doses. I found it immensely interesting and it made sense to start investigating the clinical potential of these types of drugs myself.

Addiction obviously has a huge public health impact. Why are you interested in alcohol-related issues and treatments in particular?

I’m interested in addiction in general but for me alcohol, which is a very common, devastating addiction throughout the world, was a logical place to start. As I learned when I started investigating the topic, a considerable amount of research on the use of psychedelic treatment (mainly LSD) and alcohol had already been conducted in the late 1950s.

In the United States, the Alcoholics Anonymous (AA) philosophy is prevalent in addiction treatment. It’s a philosophy that emphasizes the spiritual component of the addiction process and the importance of becoming healthier spiritually in order to recover. This also interests me.

What are the benefits of using psilocybin over LSD in a study?

Psilocybin has two practical advantages. For one, the duration of action is significantly shorter, in the order of six hours instead of ten with LSD. This makes psilocybin easier to use in an outpatient model. In other words, you can administer it in the course of a normal workday, whereas LSD sessions could easily continue late into the evening. Another important reason is that there is much more stigma attached to LSD. Many people think of LSD as a very dangerous and frightening drug. Certainly in the 1960s, there were many adverse reactions to LSD. Much of this had to do with taking extremely high doses of a substance with unknown potency, as well as a lack of understanding at the time about how important setting was in determining an experience’s outcome. Clinically speaking, both LSD and psilocybin appear to be very safe when used under carefully controlled research conditions. Also, even though the psilocybin we administer is actually a synthetic version, people often think of the substance as “mushrooms” or a naturally occurring compound, which is reassuring to some people.

Could you generalise about what types of persons were interested in joining this trial?

We recruited from the community, using advertisements aimed specifically at people who were not engaged in treatment. We wanted this to be a stand-alone treatment. We required people to be alcohol dependent, in general good health, and not suffering from any serious psychiatric illness. In our Albuquerque study, participants were working and had some intact social structure or support. They had been alcohol-dependent for an average of 15 years, the mean age was 40, and there were six men and four women. Some had limited amounts of experience with psychedelics in the past, but we excluded those with extensive use.

One concern was that people might volunteer because they wanted a psilocybin experience. We wanted to attract those seriously interested in changing their drinking and open to the possibility of novel treatments.

Can you describe the setting you provided for your patients?

The outpatient clinic was set up to look as much as possible like a comfortable living room with a large couch. We asked participants for most of the session to wear eyeshades and headphones – there was a standard program of music – and instructions were to focus on their internal experience, to accept and explore whatever came up. We prepared them for what they might experience during sessions, what the possible range of experiences could be, and advised them to manage those experiences in order to make the most of them. We believed that setting an intention was important. In this context, the general intention might have been to use the session to learn or experience something to help them make a positive change in drinking or other issues related to drinking they wanted to explore. There was very little direct intervention. Two therapists provided support and were available to intervene when needed, otherwise they checked in every 30 minutes to an hour to make sure the participant was doing okay. At the end of that session, the participants could start talking about what they had experienced. (The volunteers received psilocybin in one or two supervised sessions; this was in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions, ed.)

In some of the initial LSD trials, the therapists’ aim was to recreate an experience akin to delirium tremens (DT), a severe withdrawal symptom sometimes experienced by alcohol-dependent patients. These DTs were often a turning point for alcoholics, and they felt LSD could have similar consequences. What they found was that some participants had mystical, transcendent experiences that affected their long-term behaviour. Could you describe how peak experiences affected the patients in your study?

On a psychological and biological level, we don’t have theories, let alone data to explain these phenomena. In the context of a person trying to address a problem and make a kind of change, what we’ve seen is that participants often have an experience of oneness, the hallmark of a mystical experience. They have a sense of unity with all of creation or the universe or God, and they also have a very powerful experience of love and connection on a deep emotional level. This includes self-love and self-compassion, that feeling of being okay. This sounds almost trivial, but for some of these folks who’ve experienced a lifetime of feeling unloved, it’s a very powerful experience. In some cases, they told us their drinking had been motivated by the lack of feeling loved or lovable, and that this experience made them feel less like they needed to drink for that reason.

Other changes accompany this kind of experience. People emerge with a sense of optimism that change is possible, that life can be different because they have experienced something that is so different from anything they could have imagined. We’ve seen people spend a lot of time during sessions thinking about family and relationships, about the grief, guilt and harm their drinking has brought to others, as well as themselves. People emerge from sessions talking about pro-social values like being a good parent or contributing to society. We’ve measured significant decreases in craving and an increase in confidence that they will be able to make a change in their drinking.

How can taking a drug once or twice cause lasting behaviour change? What evidence speaks to this question?

I don’t really have an answer. Clearly things are going on in the brain and we are beginning to conduct studies that look at brain function using MRI scans before and after the psilocybin sessions. But we can’t say yet why a single acute experience can produce such lasting changes.

The best analogy we have come up with is Post Traumatic Stress Disorder (PTSD), in which a single traumatic event can impact someone’s day-to-day experience. These traumas can be of a purely psychological nature, though they often involve physical violence as well. PTSD is an example of how an acute event can cause persistent psychological and measurable biological changes in brain function and structure. Maybe what we are seeing with psilocybin is something like the opposite of PTSD—an experience so powerfully positive it can actually make lasting impact on one’s psyche and brain.

Addiction is a misguided search for spirituality. Can you comment on this or elaborate?

Carl Jung is really the person who expanded on this idea, which was that through intoxicants people (in some limited way) were able to experience connection, unity, a sense of wellness and being loved. You can think of it as a misguided search for mystical or human connection, a way to experience a reliable emotional attachment to something external in order to receive comfort. This can be a useful way of understanding and reframing people’s struggle with addictive substances as not simply seeking hedonistic pleasure, but a genuine desire for wholeness. Though if this isn’t found in healthier ways, it can readily become a trap.

The outcome of your study seems to be very promising: all of the patients experienced a definite improvement. However it was a small sample. Do you have plans to do another clinical trial?

This was a small trial without a control group, done to demonstrate the feasibility of conducting such a study. We were able to demonstrate clinical improvement, and the degree of improvement correlated with the strength of the subject’s experience during sessions. It is suggestive and by no means conclusive or convincing evidence. We need to do much larger controlled trials. Our current trial aims to recruit 180 alcohol-dependent patients, which will provide a much more rigorous test of efficacy. This will take a few years—we estimate five—to complete the trial.

Do you think there may be obstacles other than scientific that might bring psychedelic research to a halt all over again? Or do you think it will evolve into standard practice?

We understand these drugs better scientifically than we did in the 1960s, in terms of effects, potential dangers, and how to minimise those dangers in a clinical research setting. The people doing clinical research with psychedelics now are serious, experienced scientists who approach their work cautiously and with scientific rigour. The general public also has a much better understanding of psychedelics than it did 50 years ago. We need to stay balanced in our approach and avoid extrapolating beyond the data, guard against exaggerated claims and expectations, and remind people of the significant risks that exist with these drugs when used outside of structured and controlled settings.

While I and others in the field are hopeful that what we discover will lead to important advances in addiction treatment, no drug is a magic cure. There are limitations to any treatment. Addiction is a complex, chronic disorder and you cannot cure everyone in one or two sessions, nor reduce the risks to zero. But it’s reasonable to hope that we will be able to demonstrate reproducible benefits, and learn a lot about the psychology and biology of behaviour change in the process.

22 May - Delivering Effective Psychedelic Clinical Trials

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