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Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelics that are candidates for the treatment of psychiatric disorders.

 Both agents stimulate serotonin 5-HT2A receptors; LSD also acts at dopamine D13-3 receptors, and the active metabolic of psilocybin (psilocin) inhibits the serotonin transporter.

 The similarities, acute effects, and dose equivalence of these agents in humans remains unclear.

 directly compared the acute subjective, autonomic, and endocrine effects of LSD and psilocybin at 2 doses and placebo within the same participants. The acute subjective effects of these agents were assessed with validated psychometric instruments, and pharmacokinetic data were obtained over 24 hours. The investigators performed a double-blind, placebo-controlled crossover study with 5 experimental test sessions (placebo, LSD 100 µg, LSD 200 µg, psilocybin 15 mg, psilocybin 30 mg), with a washout period of at least 10 days between sessions.

The authors recruited 28 healthy participants; their mean age was 35 years and 50% were male. Exclusion criteria were: age less than than 25 years or greater than 65 years, pregnancy, family history of major psychiatric disorders in first-degree relatives, current psychotropic medication use, acute or chronic physical illness, tobacco smoking of more than 10 cigarettes/day, lifetime illicit drug use exceeding 10 times (except use of tetrahydrocannabinol [THC], the principal psychoactive cannabinoid of cannabis), or illicit drug use in the past 2 months or during the study period. In terms of previous drug use, 11 participants had previously used LSD and 6 had previously used psilocybin; 13 had previously used a stimulant; and 10 participants had no history of noncannabis illicit drug use. LSD was administered as an oral solution and psilocybin as an oral capsule. A double-dummy method was used such that participants received 6 capsules and 2 solutions at each test session.

Each test session lasted 25 hours and was conducted in a calm hospital room. Abstinence from illicit drugs was verified with a urine drug screen. Outcomes were repeatedly assessed for 24 hours. Standardized meals were served. An investigator was present in the room during the acute effect phase and remained in a room next to the participant for up to 24 hours. Subjective effects were assessed repeatedly using visual analogue scales (VAS), the Adjective Mood Rating Scale (AMRS), the 5 Dimensions of Altered States of Consciousness scale (5D-ASC), and the Mystical Effects Questionnaire(MEQ). Effect durations were assessed using the classic pharmacokinetic-pharmacodynamic link module. Blood pressure, heart rate, and temperature were repeatedly measured. Adverse effects were assessed 1 hour before and 12 and 24 hours after drug administration. Plasma LSD and psilocybin concentrations, and cortisol, prolactin, oxytocin, and brain-derived neurotrophic factor (BDNF) measurements were also obtained at multiple time points. Pharmacokinetic parameters were estimated using noncompartmental methods. Peak drug effects (minimum, maximum, or change from baseline) were determined for repeated measures, then analyzed using repeated-measures analysis of variance.

Both doses of LSD and the 30-mg psilocybin dose produced comparable subjective effects, based on VAS and 5D-ASC outcomes. There was significantly greater ego dissolution and a trend toward greater anxiety with 200 µg versus 100 µg LSD. Psilocybin 15 mg had significantly lower effects than psilocybin 30 mg and both LSD doses, based on VAS and 5D-ASC outcomes. Both LSD doses had significantly increased “emotional excitation” on the AMRS compared with psilocybin. There were no differences in subjective effects of LSD or psilocybin based on sex.

Both LSD and psilocybin significantly increased systolic and diastolic blood pressure, temperature, and pupil diameter compared with placebo. Psilocybin 30 mg produced significantly greater increases in blood pressure and temperature compared with psilocybin 15 mg and both doses of LSD. By contrast, both LSD doses produced a greater increase in pulse compared with both psilocybin doses and placebo. Psilocybin produced greater impairments in pupil contraction compared with LSD. Both LSD and psilocybin increased the total acute (0-12 hours) adverse effect score compared with placebo. Subacute (12-24 hours) adverse effect scores were significantly greater with LSD 200 µg LSD and psilocybin 30 mg compared with placebo. The most common adverse effects were headaches. Five participants had 9 flashback episodes within 72 hours. No severe adverse events were observed.

Both LSD doses had significantly longer effect durations (10-11 versus 6-7 hours) and earlier onset of effects (0.4-0.6 versus 0.8 hours) compared with both psilocybin doses. The elimination half-life values were about 4 hours for LSD and 2.5 hours for psilocybin. Both LSD and psilocybin significantly increased plasma cortisol, prolactin, and oxytocin levels, but neither affected BDNF levels. Both LSD and psilocybin showed linear pharmacokinetics, which were not influenced by body weight.

In terms of blinding, no clear distinction between LSD and psilocybin could be made after the session or at study end point. Participants correctly identified the psychedelic and dose in about 60% of sessions, compared with 96% for placebo.

The authors investigated and directly compared the acute effects of LSD and psilocybin in healthy participants in a well-blinded study. They concluded that psilocybin 15 mg exerted clearly weaker subjective effects, and both agents had dose-dependent effect durations (significantly longer for LSD), stimulant autonomic effects, and increased endocrine parameters. Body weight had no influence on blood concentrations. The investigators noted the data further supported the notion that states of consciousness alteration induced by LSD and psilocybin are more likely dose-dependent rather than substance-dependent. In addition, they concluded the differences in the pharmacological profiles of LSD and psilocybin do not relevantly influence subjectively experienced effects of both psychedelics.

Study strengths included the within-subjects design and the use of well-characterized, fixed dosing. The primary study limitations were the use of a highly controlled setting and the participation of healthy participants only.

This study supports dose finding for research and psychedelic-assisted therapy. Psilocybin 20 mg is likely equivalent to LSD 100 µg. There was no evidence for qualitative differences in altered states of consciousness, except for a shorter duration of action for psilocybin.

 is a professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is on the Editorial Board and serves as the schizophrenia section chief for 

. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

1. Carhart-Harris R, Giribaldi B, Watts R, et al. 

Trial of psilocybin versus escitalopram for depression.

2. Griffiths RR, Johnson MW, Carducci MA, et al. 

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial.

Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial.

LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: a qualitative study of acute and sustained subjective effects.

5. Rickli A, Moning OD, Hoener MC, Liechti ME. 

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens.

Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects.

In a well-blinded study, researchers investigated and directly compared the acute effects of LSD and psilocybin in healthy participants.  

Effects of LSD and Psilocybin in Healthy Participants

The “cab driver test” is a convenient metric of sentiment analysis to determine when a treatment or product has reached a hype cycle. For example, when your cab driver is advising you on experimental drug infusions or supplemental enemas, the information available to the public is probably beyond the purview of the specialists. For 

, the equivalent could be that when Gwyneth Paltrow produces a 

 episode on the subject, the space has slipped out of the control of academia and science and is significantly being directed by market forces. It is no longer a “field”—it is now an “industry.”

These forces that dictate the direction in which the industry will grow and mature have shifted beyond the organicity of academic cadence. A keen eye would note the significantly disproportionate development of the industry: Of the 73 biggest companies in the psychedelic industry that have taken in $3.26 billion in capital, $2.9 billion is in drug development.

 This is unsurprising considering the valuation multiples and revenue growth of pharmaceuticals compared with the other subsectors in the psychedelic ecosystem, including clinics, therapist training, and true academia.

Although most of the industry seems intent on developing novel and patentable psychedelic substances, a key factor that appears largely overlooked by the growth wave is, as one of the most prominent researchers in this field, Robin Carhart-Harris, PhD, titled his 2018 paper, “the essential importance of context.”

Context, more commonly described in the psychedelic field as “set and setting,” refers to the careful preparation of the patient mindset before and while they go into the psychedelic session, along with the physical setting in which the dosing takes place—the structure, music, decor, and other environmental components. However, that is but the obvious, floating tip of the contextual iceberg.

Context is a multifaceted, all-encompassing construct encapsulating treatment setting, therapeutic relationship, cultural milieu, historical inclinations, and social attitudes. Although therapist proficiency is key to therapeutic sessions and drug development modulates the experiential moments of the psychedelic session, context is the only factor that works to support both the psychedelic-based and the therapist-based components. The critical role it plays in treatment is far from unique to the psychedelic field.

If we consider the standard frontline pharmacological treatments for anxiety disorders, selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, these drugs do not ameliorate mental illness via a single dose, nor does their continued use in isolation provide a “cure” for mental distress. Despite the many drug treatments that are available, many patients do not respond to initial treatment or even to sequential trials of differing medications.

According to an FDA meta-analysis of antidepressant effects from 15 years ago

“Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.”

In response to that, Christoph Hiemke, PhD, wrote

“Current knowledge indicates that effects of antidepressant pharmacotherapy are a sum of nonspecific effects, placebo effects, and pharmacological effects….It is proposed that 3-armed studies in which participants are assigned to either drug, placebo, or no treatment enable to measure exactly the differential effect sizes of drug and placebo. Such studies, however, do not exist so far.”

According to personal correspondence from Luke Downey, PhD, a professor and head of the Drugs and Driving Research Unit at the Centre for Human Psychopharmacology at Swinburne University of Technology in Melbourne, Australia:

“A host of reasons are implicated in the relative efficacy of these pharmaceutical treatments, and even in the cases where treatment is effective, these clinical improvements do not occur in isolation. The effects of these drugs when used in a supportive context are very important. They give patients the opportunity to benefit from other treatments and interventions including cognitive-behavioral therapy, mindfulness meditation, guided imagery with relaxation, solution-focused therapy, and coping skills and other education that address both symptoms of mental illness and triggers of distress. These nonpharmacological factors such as client-therapist relationship and the setting of any clinical intervention are considered key moderators of efficacy in psychiatry just as the developing field of psychedelic-assisted psychotherapy needs to consider modifiable components of this treatment.”

Is It Time for Psychedelic-Assisted Psychotherapy to Embrace Technology?

According to William A. Richards, “Those who have known these profoundly meaningful states of consciousness have often shared them with no one, or only with those most intimately trusted, for fear of being misunderstood, called 

 At the core of the psychedelic-based treatment is its capacity to tap into noncognitive, experiential, emotional, and embodied processes of healing, which are far more difficult to achieve with talk therapy.

In his recent thesis titled, “Integrating the Ineffable: A Social Phenomenological Analysis of the Psychedelic Experience,” Logan Neitzke-Spruill stated that, “The common understanding of the experience as ineffable may indicate a general lack of affirmative frameworks for integrating these experiences.”

In the words of Hamilton, one of the individuals who provided a narrative account of his experience with psychedelics, which were collected and published by Timothy Leary, “The experience is so fantastic in both its novelty and its power as to beggar all possibility of adequate depiction through words. The most that can be hoped for by way of description is an approximation, and only those who have had the drug can know how far removed from actuality the approximation must be.”

When we consider this in depth, the psychedelic experience appears to have more parallels with the virtual reality (VR) experience than with talk therapy. Both create an intimate, personal space for healing and introduce the patient to an alternate reality, and both experiences are characterized by ineffability. Utilizing those synergistic properties to explore and integrate the psychedelic experience allows more time for the emotional, embodied, experiential narrative to unfold, before it is analytically and logically processed. The psychedelic treatment model empowers patients to take responsibility for their own healing. The unique therapeutic process returns agency over one’s mental health to the individual.

 has always enabled distribution of power. It allows new perspectives on existing problems, often guiding our progress in ways we could not have expected. We develop tech, which, in turn, reshapes us. One of the powerful, robust tools that appears to be uniquely suited for contextual design that supports the intimate, patient-driven pathway of recovery—sometimes referred to as “the inner healing intelligence”—is VR.

At the University of Bristol, a team of computer scientists led by David R. Glowacki, PhD, concluded their study on immersive VR environments: “It is possible to design phenomenological experiences using multiperson VR, which create the conditions for mystical-type experience from which participants derive insight and meaning.”

The first-ever research study on combining VR with psychedelics was recently conducted by the authors in collaboration with Swinburne University of Technology and Psychedelic Society Belgium. Participants of this retreat-based study, which used psilocybin-containing truffles along with a bespoke anchoring VR designed by Enosis Therapeutics, reported that “VR brought me back to the feeling of something ineffable and a feeling of knowing,” and “VR soothed me before the talk integration process. It contributed to the sense of wonder and authenticity, and when you grab the stars, it feels beautiful.”

Those synergistic, state-altering properties can be easily taken advantage of in therapy. For example, VR expands the mode of self-expression beyond current analog means with immersive, 3-dimensional tools or personalized spatial designs of the VR model, which can be used to create representations of thoughts, insights, or emotions experienced during the psychedelic session. 

What is interesting and perhaps less obvious about this approach is that, while VR allows for a greater range of creative expression, the process of self-expression in a virtual environment also seems to challenge familiar modes of perception and activate a full-sensory engagement,

 reacquainting the patient to the experience of an altered state of consciousness. The intimate world of VR, which can be accessed without therapist interference, grants patients the unique opportunity of a space that can be used to explore and consolidate psychedelic experiences before they need to be verbally shared or discussed with another human being.

Technology leapfrogs many limitations of the analog system by offering an infinite number of levers with which to modulate the contextual design. This means that an entire range of possible solutions can be first thoroughly explored before settling on the best methodology. For example, in the current therapeutic model, patients transition from full visual range to having blindfolds on for the bulk of the psychedelic dosing session—an “all or nothing” model of stimuli exposure. 

VR allows for controlled dosing of stimuli, providing an entire spectrum of stimuli intensity, complexity, range, and duration. Just as important, it allows individual control over the stimuli that form setting design (via individualized VR environments), as well as the ability for rapid shifts in setting to correspond with volatility of the patient’s psychoemotional state.

According to Carhart-Harris, “Remarkably, despite its widespread adoption among psychedelic researchers, few controlled studies have ever been performed to test the assumed relationship between psychedelics and context.”

 Despite the apparent prioritization of “set and setting” in psychedelic research, the focus of innovation in the field is significantly skewed toward drug development while environmental and contextual factors are largely neglected.

In contrast to other medical fields, the human-technology interface is poorly explored in mental health care and almost entirely ignored in psychedelic care. A continued lack of dialog around the idea that technology could be a compatible resource rather than a competitive, counterproductive agent perpetuates the opportunity cost of the unmet potential of optimized healing environments in psychedelic treatment.

We believe that introducing technology allows an efficient and in-depth exploration of diverse contextual elements, which is of particular importance to a field that is only just beginning to take shape. This helps mitigate the risk of this paradigm-shifting approach to mental health treatment being shoehorned into incumbent psychotherapeutic models. A robust exploration and understanding of the altered-state experience should be the process driving the development of therapeutic frameworks that are designed around that experience—not the other way around.

is cofounder of Enosis Therapeutics and a PhD researcher at Swinburne University of Technology in Melbourne, Victoria, Australia. 

is cofounder of Enosis Therapeutics; founder of digital currency brokerage Caleb & Brown; and a clinical adviser to the Australian Psychedelic Society.

1. Psychedelic sector overview: opening remarks. Psychedelic Alpha. Accessed June 20, 2022. 

https://psychedelicalpha.com/psychedelic-sector-overview

2. Carhart-Harris RL, Roseman L, Haijen E, et al. 

Psychedelics and the essential importance of context

3. Kirsch I, Deacon BJ, Huedo-Medina TB, et al. 

Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration

Why do antidepressant therapies have such a poor success rate?

Sacred Knowledge: Psychedelics and Religious Experiences

Integrating the Ineffable: a Social Phenomenological Analysis of the Psychedelic Experience

. Master’s thesis. University of Delaware; 2019

7. Leary T. Timothy Leary: series IV. New York Public Library Digital Collections. Accessed June 20, 2022. 

https://digitalcollections.nypl.org/collections/timothy-leary-papers#/?tab=about

8. Glowacki DR, Wonnacott MD, Freire R, et al. Isness: using multi-person VR to design peak mystical-type experiences comparable to psychedelics. Paper presented at: ACM CHI Conference on Human Factors in Computing Systems; April 25-30, 2020; Honolulu, HI. Accessed July 11, 2022. 

https://research-information.bris.ac.uk/en/publications/isness-using-multi-person-vr-to-design-peak-mystical-type-experie

Virtual reality as a moderator of psychedelic-assisted psychotherapy

10. King JL, Kaimal G, Konopka L, et al. 

Practical applications of neuroscience-informed art therapy

How can a robust understanding of the altered-state experience drive the development of therapeutic frameworks that are designed around that experience?

Challenging the Status Quo of the Challenge to the Status Quo

Does a health care provider’s sex impact how well active agents perform? The answer appears to be a “yes,” according to a new study that examined the antidepressant response to ketamine and its bioactive metabolite (

)-hydroxynorketamine when the drug was administered to mice by men compared to women.

Todd Gould, MD, study coauthor and professor of psychiatry at the University of Maryland School of Medicine, and colleagues decided to study the relationship between mouse response to ketamine and the sex of the ketamine administrator when they noticed anecdotally that mice only seemed to respond consistently to ketamine when it was administered by a male researcher. When they reached out to other labs that were studying mouse response to ketamine, they learned that other labs had noticed the same thing, but had not systematically documented the phenomena or investigated potential causes.

So, the authors tested the phenomena by having both men and women rub cotton swabs and T-shirts on a wrist or elbow or behind an ear, and then placing the swabs and shirts among the mice to see which scent the mice preferred to be around. They noted that the mice preferred to be around the swabs and shirts that came from women—however, when they incorporated a chemical to block the smell of the mice, the mice no longer showed a preference for the women’s swabs or shirts.

After verifying these findings in a large systematic experiment, the authors investigated the mechanism that causes this behavior in mice.

They determined that the scent aversion and stress susceptibility in the mice was mediated by the activation of corticotropin-releasing factor (CRF) neurons within the entorhinal cortex that project into the hippocampal area CAI

—the region of the brain responsible for memory and learning that had been previously associated with depression.

When the authors had female researchers administer the ketamine with an injection of CRF, the mice began responding to the antidepressant effects of the ketamine.

“Our findings in mice suggest that activating a specific stress circuit in the brain may be a way to improve ketamine treatment,” Gould said in a press release. “Our thought is that you may be able to provide a more robust antidepressant effect if you combine the ketamine with activation of this brain region, either a drug that spurs this process in the brain or even some sort of specific stressor.”

Although these findings are not directly relevant to the human response to ketamine, the authors stated that the underlying brain mechanism may be useful in determining why some patients do not respond well to ketamine therapy and potentially in helping clinicians adjust the therapy for greater effectiveness in these patients.

“We think that some people may have higher or lower levels of CRF, and we believe that people who do not respond well to ketamine antidepressant therapy might respond if we could administer the treatment with some CRF-related chemical that could induce ketamine’s effects,” said Polymnia Georgiou, PhD, study leader and former postdoctoral fellow in Gould’s lab, in a press release. “Alternatively, we typically see the antidepressant effects of ketamine lasting 1 to 3 days, but with CRF administration, it is possible that we may be able to extend the effects to last longer with CRF.”

1. Drug effects of ketamine in mice can depend on the sex of the human experimenter. University of Maryland School of Medicine. News release. August 30, 2022. September 13, 2022. 

https://www.newswise.com/articles/drugs-effects-of-ketamine-in-mice-can-depend-on-the-sex-of-the-human-experimenter

Experimenters’ sex modulates mouse behaviors and neural responses to ketamine via corticotropin releasing factor

The underlying neural mechanisms identified may help clinicians better understand ketamine response in human patients.

Study Explores Effects of Experimenter Sex on Ketamine Response

A new phase II trial, STOP (Study of the Treatment of Overeating Using Psilocybin), is currently underway to determine the efficacy of psilocybin candidate TRP-8802 in combination with psychotherapy for the treatment of binge eating disorder (BED). To learn more about this research, 

™ sat down with Jim Gilligan, PhD, MBIS, the chief science officer and interim CEO of Tryp Therapeutics.

PT: Can you say a bit more about the aim of the study and how TRP-8802 might change treatment for individuals with BED?

 The use of psychedelics in conjunction with psychotherapy provides clinicians with a tool to reach deeper into the patient’s subconscious and potentially gain a better perspective on what is driving the aberrant behaviors with respect to eating. Overeating disorders can be viewed in part as addictive behavior relating to food.Psychedelics and psilocybin, in particular, have shown benefit in treating patients with addictive behavior.

In addition, patients with BED often also experience anxiety around food and depression, which might be considered comorbidities. Psilocybin has also shown promise in patients with both anxiety and depression. It is important to recognize that a change in the patient’s behavior is of paramount importance. For instance, a significant portion of patients that seek bariatric surgical intervention achieve an immediate benefit, but over time gain back weight because their behavior towards food has not changed. The neuroplasticity potential of psilocybin, in conjunction with psychotherapy, has the potential to “rewire” these behaviors and improve the patient’s behavior toward food.

PT: Why specifically BED? Do you think this could have an effect on eating disorders as a broader category?

Binge eating is typically viewed as a loss of control type of eating disorder that is extremely socially limiting and causes feelings of guilt for the individual. These characteristics make it an ideal candidate for psilocybin therapy for eating disorders, as it has been shown that psilocybin can help other “loss of control” psychiatric issues, like OCD and alcoholism. Binge eating is the most prevalent eating disorder, and many experts have noted that it is underrecognized and undertreated. What we learn about psilocybin assisted therapy in BED could have relevance for other eating disorders. There is some overlap in clinical presentation such as body dissatisfaction as well as links to histories of trauma in some patients with eating disorders.

There is a level of commonality among the different eating disorders, and we believe that psilocybin treatment in conjunction with psychotherapy could have a positive effect on other types of eating disorders. Psilocybin is also currently being examined in clinical programs in patients with anorexia nervosa.

PT: Approximately 10 million boys and men in the US will experience an eating disorder at one point in their lives. How do you think this research will specifically impact men/boys?

Binge eating is the most common eating disorder among men, so this research may have special relevance to this population. Our study will include men with binge eating disorder, so hopefully, the results will be able to be generalized between sexes and not limited to males or females exclusively. Psychedelics have never been tested in BED for men or women previously. These preliminary results will hopefully provide useful information for future studies that examine this topic more closely.

PT: What are some of the differences in presentation/symptoms among the sexes, and how does psilocybin impact those?

Men tend to be more secretive and in denial about binge eating, so it is a bit more difficult to get them to be open to change and forthcoming about what is going on in their lives. Psilocybin can potentially make them more open to dealing with the issue internally and more accepting of therapy.

This denial by men may also partially account for why there is a greater prevalence of BEDs in females than males (about a 2:1 ratio). However, there are more similarities than differences in clinical presentation across the sexes. We do not know yet how psilocybin impacts clinical presentation and other outcomes across the sexes, but hopefully, the current research will set the stage for larger studies.

PT: Both psilocybin and eating disorders, especially in men, unfortunately, carry a stigma. Do you think this new research can help lessen that stigma?

Hopefully, this research will reduce the stigma. Again, both sexes are being studied in this study. The research may help change the view of psilocybin in general to one that sees it as medicine or curative. This research, in combination with the rapidly expanding field of psychedelic science, may go a long way towards reducing this stigma.

PT: What about the issue of dosage? With orally administered psilocybin, there can be a thin line between a clinical dose and a bad trip.

Tryp recognized early on the variability in response to orally administered psilocybin. Published pharmacokinetics results revealed that even when administered on a weight-adjusted basis (mg/kg), there was up to a 4-fold range in blood levels which could contribute to some individuals not achieving a meaningful psychedelic experience, while others had a “bad trip.” Other deficiencies associated with oral administration include the lapse in time between oral dosing and the start of the psychedelic experience, which can take up to 2 hours, and the length of the trip, which could be another 6 to 8 hours and can potentially be burdensome to the patient and clinicians alike.

There is a safety-related issue as well with oral dosing. There is a “loss of control” of the oral dosage form, meaning once you take the capsule you lose control over what will happen should there be a safety concern. TRP-8803, which is Tryp’s proprietary psilocybin, addresses all of these limitations. TRP-8803 has the ability to induce the psychedelic state within ~30 minutes while accurately targeting blood levels known to induce the psychedelic state, is also shown to be safe, and has the ability to control the length of the experience and terminate if necessary.

PT: What should clinicians know about the use of psilocybin for treating patients with binge eating disorder?

The results from this study may help inform clinicians in the future on the potential role of psilocybin in conjunction with psychotherapy in the treatment of BED.

is the chief science officer and interim CEO of Tryp Therapeutics.

This new study is evaluating how effective psychedelics can be in the treatment of binge eating disorder. 

Psychedelics for the Treatment of Binge Eating Disorder in Males

To read the article, please see the September Supplement to 

Bandeira ID, Lins-Silva DH, Cavenaghi VB, et al. 

Ketamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review

Antidepressant effects of ketamine in depressed patients

Feder A, Parides MK, Murrough JW, et al. 

Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial

Observation of Distressed Conspecific as a Model of Emotional Trauma Generates Silent Synapses in the Prefrontal-Amygdala Pathway and Enhances Fear Learning, but Ketamine Abolishes those Effects

Mathew SJ, Murrough JW, aan het Rot M, Collins KA, Reich DL, Charney DS. 

Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial

Newport DJ, Carpenter LL, McDonald WM, et al. 

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Niciu MJ, Ionescu DF, Richards EM, Zarate CA Jr. 

Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder.

Rodriguez CI, Kegeles LS, Levinson A, et al. 

Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept

Zarate CA Jr, Singh JB, Carlson PJ, et al. 

A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression

Numinus' Chief Clinical Officer shares resources about the potential use of ketamine in psychiatry.   

Numinus Resources

The first patient received a dose of a pharmaceutically optimized form of lysergic acid diethylamide (LSD) in the phase 2b dose-optimization trial for MM-120 for the treatment of generalized anxiety disorder (GAD), according to biopharmaceutical company MindMed.

"The initiation of our phase 2b clinical trial, the largest well-controlled clinical trial of LSD ever conducted, represents a major milestone for MindMed and for the many patients suffering from GAD," said Robert Barrow, Chief Executive Officer and Director of MindMed. "This exciting next step in the advancement of LSD builds on the positive topline data presented by our partners at University Hospital Basel in May 2022, which demonstrated the rapid, durable, and statistically significant effects of LSD and its potential to safely mitigate symptoms of anxiety and depression. The results of our phase 2b trial will guide the dose selection and development strategy for our pivotal phase 3 clinical trials, as we continue our efforts to bring a new potential treatment to the millions of people living with GAD."

The phase 2b trial is a multi-center, parallel, randomized, double-blind, placebo-controlled, dose-optimization study. Investigators plan to enroll 200 participants who will receive either a single administration of up to 200 µg of MM-120 or placebo. The primary objective is to determine the reduction in anxiety symptoms 4 weeks after a single administration of MM-120, compared across the 5 treatment arms. Key secondary objectives, measured up to 12 weeks after the single administration, include assessments of safety and tolerability as well as quality of life.

Earlier this year, the American Psychiatric Association put out its official statement on psychedelics, encouraging research of this kind: “There is currently inadequate scientific evidence for endorsing the use of psychedelics to treat any psychiatric disorder except within the context of approved investigational studies. APA supports continued research and therapeutic discovery into psychedelic agents with the same scientific integrity and regulatory standards applied to other promising therapies in medicine.”

If you are interested in reading more about psychedelics, check out our February front cover “

Psychedelics and the Future of Psychiatry

,” and coverage from our recent 2022 Annual Psychiatric Times™ World CME Conference, “

The Recent Resurgence of Psilocybin: Is It Here to Stay?

™ Psychedelic Supplement, coming in September.

1. MindMed announces first patient dosed in phase 2b trial of mm-120 in generalized anxiety disorder. News release. PR Newswire. August 25, 2022. 

https://www.prnewswire.com/news-releases/mindmed-announces-first-patient-dosed-in-phase-2b-trial-of-mm-120-in-generalized-anxiety-disorder-301612131.html

2. Position statement on the use of psychedelic and empathogenic agents for mental health conditions. American Psychiatric Association. July 2022. Accessed August 25, 2022. 

https://www.psychiatry.org/getattachment/d5c13619-ca1f-491f-a7a8-b7141c800904/Position-Use-of-Psychedelic-Empathogenic-Agents.pdf

The first patient has been dosed in the phase 2b dose-optimization trial of a pharmaceutically optimized form of LSD for the treatment of generalized anxiety disorder.

First Patient Dosed in Trial of LSD for Generalized Anxiety Disorder 

This is the extra table for "Interest Grows in Treatment of Mood Disorders by Classic Psychedelics."

Figures for Interest Grows in Treatment of Mood Disorders by Classic Psychedelics

“Two thirds of the sample said that their psilocybin experience was among the top 5 most meaningful of their entire lifetimes,” shared David B. Yaden, PhD, assistant professor in the Center for Psychedelic and Conscious Research at Johns Hopkins University School of Medicine.

Yaden, in his presentation on “The Evidence for Psychedelics in Psychiatry” at the 

2022 Annual Psychiatric Times™ World CME Conference

 in San Diego, shared that serotonin molecules actually look quite similar to LSD and psilocybin—thus, serotonergic hallucinogens. “In vitro and in vivo, classic psychedelics increased neurite growth, spine density, and synaptogenesis. For this reason, some of them call these substances psychoplastogens.”

Yaden explained that set and setting for a psychedelic administration session, as the mindset and expectations that an individual brings to the experience, as well as the physical location, can impact the acute subjective effects. “Not all psychedelic experiences are good or euphoric—far from it,” Yaden said.

In a survey of 1993 individuals meant to gauge their single most psychologically difficult or challenging experience—or worst “bad trip”—after consuming psilocybin mushrooms, 39% rated the experience as among the top 5 most challenging experiences of their lifetime, 11% reported putting themselves or others at risk of physical harm, and 2.7% reported getting medical help during the event.

 Despite this, in another study, psilocybin was lowest rated in terms of likelihood of harm to self and others compared to other substances.

In one open-label study, psilocybin was correlated with sustained and substantial decreases in depression.

 These results were replicated in further studies.

“It’s also the only substance type among all of these recreational-use substances that is associated with lower suicide attempts,” Yaden said.

As to how Yaden and his investigative team conducts his research, he explained the process. First, participants must go through a “quite intensive medical psychological screening” to reduce generalizability of these studies. Then, there are a number of preparatory sessions to build rapport and provide psychoeducation, followed by experimental sessions where psilocybin is administered. In these sessions, the participant is lying down on a couch with eyeshades and headphones. Two therapists are always in the room, and the sessions are always recorded. Participants can ask for a therapeutic touch, or a hand to hold. Afterwards, integrative sessions allow participants to discuss their experience.

“Many people use metaphors like climbing a mountain or running a marathon,” Yaden said. “They involve challenge and difficulty, but also moments of meaning and joy.”

Yaden believes this signals that psilocybin is worth further study. “This is controversial; we are trying to figure this out. I think it is important not to rush to a simplistic story, as we are learning from the process. There is evidence for a number of possible therapeutic mechanisms and emotional processing—social, self, and behavioral.”

Psychedelics promote structural and functional neural plasticity.

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Survey study of challenging experiences after ingesting psilocybin mushrooms: acute and enduring positive and negative consequences.

3. Nutt DJ, King LA, Phillips LD; Independent Scientific Committee on Drugs. 

Drug harms in the UK: a multicriteria decision analysis.

4. Carhart-Harris RL, Bolstridge M, Rucker J, et al. 

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

6. Carhart-Harris R, Giribaldi B, Watts R, et al. 

One researcher shares his evidence for the usage of psilocybin in psychiatry. 

John J. Miller, MD, tries to untangle the controversies around psilocybin in this video and in his talk at the 

is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief,

; Staff Psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

The resistance against "magic mushrooms"—is it justified? 

Psilocybin: The Complicated Conversation

“Too many people are suffering, and this [psychedelic] mental health revolution is so overdue,” said Reid Robison, MD. As depression continues to plague many patients, psychedelic medicine may offer a new option to clinicians and patients. Here, Robison shares his journey in discovering the promise and potential of psychedelics, and how it might hold the answer to addressing mental health care issues.

is a board-certified psychiatrist and chief clinical officer at Numinus. He has been working with ketamine in research and clinical settings for more than 12 years. He is currently principal investigator of a number of psychedelic studies, including ones looking at psilocybin and LSD. Robison previously served as a coordinating investigator for the MAPS-sponsored MDMA-assisted psychotherapy study of eating disorders.

We have an urgent need for new and improved treatment options for depression—are psychedelic medications the answer?

Psychedelics