Translational Psychedelic Research Program, UCSF

05/18/2022

TrPR has just published a new blog post, “Interactions between ketamine and prescription antidepressants”! As a party-drug-turned-“new-age”-antidepressant, ketamine has injected some pizzazz into the world of psychopharmacology. Given the high disease burden of depression and other psychiatric disorders, many are flocking to the infusion clinics in hopes of a quantum change. But what is at stake, particularly when it comes to ketamine’s safety and efficacy together with other more traditional antidepressants?

Ketamine is a dissociative anesthetic with a famously rapid onset of activity, a unique property not seen in many other prescription antidepressants that take weeks to exert their effects. It primarily acts on the NMDA receptor as an antagonist at the GABA-releasing interneurons, inducing a downstream elevation in glutamate stimulation of the AMPA receptors, which is implicated in its antidepressant properties. It also secondarily binds to opioid receptors and modulates the monoamine systems (dopamine, serotonin, norepinephrine). Its rather promiscuous binding profile, therefore, gives rise to the sensible concerns regarding its possible interactions with other pharmaceuticals, with antidepressants being the most commonly prescribed for patients potentially benefiting from off-label ketamine therapy.

Broadly, there seems to be no significant adverse interactions between ketamine and regularly prescribed antidepressants, with the exception of a few. In fact, many patients receiving ketamine infusion therapy are advised to stay on their longitudinal medication regimen whilst receiving ketamine. Check out the full blog post on TrPR’s website to learn about ketamine’s interactions with each class of antidepressants, including SSRIs, SNRIs, TCAs, MAOIs, Bupropion, Mirtazapine, Lithium, Lamotrigine, and Benzodiazepines.
https://psychedelics.ucsf.edu/blog-0.

04/13/2022

Check out TrPR's blog post from last week, “What happens when we take psilocybin?” by Melinda Wang! Many may understand psilocybin, the core psychoactive component of “magic mushrooms”, as a compound that induces powerful, mind-bending, and even theistic hallucinations - much akin to other classic psychedelics such as L*D (lysergic acid diethylamide), DMT (N, N-dimethyltryptamine), and mescaline. But what does this all mean - down at the molecular level? How do psychedelics modulate our brain? Can science close the explanatory gap between the subjective, phenomenological experiences of psilocybin and our current objective understanding of the neuropharmacology of these compounds?

Maybe, if we lend enough credence to the best approximations that science can come up with. Psychedelic research is still in its infancy, beset with a lot of epistemic issues, but so far, it has seemed to provide adequate approximations. Just in the last decade, research published by multiple academic teams and institutions have significantly furthered our understanding of psilocybin on both the experiential level and the neurobiological level. On the experiential front, three component parts exist for every experience: the visual/physical, the cognitive, and the emotional. On the neurobiological front, many state-of-the-art modalities and methodologies have enabled the mapping of these component parts to processes in the brain.

Science has given us some clues in unifying the neuropharmacological underpinning of psychedelics with the experiential. In essence, psychedelics can transiently mobilize our escape from the orbit of our ego, recondition our previous maladaptive cognitive models via engagement with new ideas and emergence of new insights, and restore us back to our sober consciousness armed with more robust models. But this still leaves much to be desired. As the field of psychedelic research becomes less and less bottlenecked by legal and financial constraints, more and more questions will surely be answered. And that is TrPR’s mission.

Make sure to check out the blog post for a full, in-depth discussion of this topic and the evidence that supports it!

Many may understand psilocybin, the core psychoactive component of “magic mushrooms”, as a compound that induces powerful, mind-bending, and even theistic hallucinations - much akin to other classic psychedelics such as L*D (lysergic acid diethylamide), DMT (N, N-dimethyltryptamine), and mescali...

03/31/2022

Last week, TrPR published a new blog post, Medical Contraindications to “Classic” Psychedelic Use by Dr. Gowri Aragam!

“Classic Psychedelics” include Psilocybin (Magic Mushrooms), L*D (Acid), DMT (Ayahuasca), and Mescaline (Pe**te). These substances are grouped together as “classic” because they all impact the same Serotonin receptors in the brain, specifically 5HT-2A [1]. These psychedelics are typically used in the setting of psychedelic assisted therapy, where a person is monitored by a clinician and guided through therapeutic questions. The doses of classic psychedelics used to treat these conditions have been found to be relatively safe overall [2]. However, this does not mean that they are safe for everyone.
A contraindication is a reason a person should not receive a particular treatment due to the risk of significant medical or psychological harm. A relative contraindication is a medication/diagnosis/symptoms that makes a treatment higher risk for a person, but could be advisable if benefits of the treatment outweigh the risks [3]. An absolute contraindication is something that cannot be used under any circumstance due to the high level of risk. Medical harm constitutes harm to a person’s physical body, such as stroke, heart attack, death, while psychological harm constitutes harm to a person’s mental health, such as psychosis, emotional dysregulation, suicidality.
The most common medical side effect of classic psychedelics is an elevation in blood pressure and heart rate. While this effect can be safe for most people to tolerate, it is dangerous for others whose bodies cannot safely handle high blood pressure. As a result, psychedelics are contraindicated if someone is pregnant, or has a history of epilepsy/other seizure disorder, or severe cardiovascular disease including uncontrolled blood pressure, heart failure, coronary artery disease or previous heart attack or stroke [3]. Because psychedelics work by activating Serotonin receptors in the brain, they can lead to a life threatening condition called Serotonin Syndrome if used in conjunction with other medications or substances that also increase Serotonin levels in the brain.

Another potential effect of psychedelics is prolonged psychosis. While this side effect is very rare in the general population, it can be incredibly dangerous for people who have a personal or family history of primary psychotic or affective disorders like Schizophrenia, Schizoaffective disorder, or Bipolar 1 disorder. It can also be dangerous for people who experience psychotic symptoms in the setting of depression.
If someone is considering engaging in psychedelic assisted treatment for a psychiatric or psychological issue, it is imperative to discuss this with a trained medical professional before use.
Check out the full blog post at https://psychedelics.ucsf.edu/blog/medical-contraindications-%E2%80%9Cclassic%E2%80%9D-psychedelic-use!

“Classic Psychedelics” include Psilocybin (Magic Mushrooms), L*D (Acid), DMT (Ayahuasca), and Mescaline (Pe**te). These substances are grouped together as “classic” because they all impact the same Serotonin receptors in the brain, specifically 5HT-2A [1]. In the past couple decades, there h...

03/21/2022

TrPR has just posted a new blog entry, “What is Psychedelic-Assisted Therapy?”. Psychedelic-assisted psychotherapy (PAP) combines talk therapy, a range of "experiential" therapies, and the use of psychedelic drugs to treat low mood, addiction, and fear-based disorders. While psychedelic drugs have been used therapeutically in a wide variety of contexts, PAP as it is practiced in the majority of FDA clinical trials follows a protocol established by Dr. Stanislov Grof. Grof's method of PAP as outlined in L*D Psychotherapy (Grof, 2008) describes the thoughtful integration of a trusting therapeutic relationship, a safe and aesthetically pleasing environment, emotionally evocative music, supportive touch, deep breathing, psycho-education, and mind-altering drugs.

PAP treatment is typically facilitated by two therapists who support patients through the entirety of their treatment. The responsibilities of the co-therapist team include describing the treatment protocol to patients, helping patients identify their goals for treatment, helping patients prepare for their experiential sessions, and answering any questions patients might have. The co-therapists maintain a calm, warm, present-focused, and quiet presence throughout the experiential session. This helps patients feel relaxed, safe and cared for while they are engaged in their drug-assisted experience.

A typical PAP experiential session begins with the patient stating their intention and ceremoniously receiving the psychedelic drug from the co-therapy team. The patient will then lie comfortably on a couch or futon, while they listen to relaxing music through headphones. The co-therapists sit close by, ready to support the patient when indicated. For most of the 6-8 hour experiential session, the co-therapists sit quietly while the participant explores the visions and emotional experiences that the psychological drug induces in their minds.

Ultimately the aim of this dynamic and integrative treatment is the long-term reduction of psychological distress and increase in the quality of daily life.

Check out the full blog post at https://psychedelics.ucsf.edu/blog-0!

02/21/2022

TrPR is currently conducting a groundbreaking PDP study, Psilocybin Therapy for Depression and Anxiety in Parkinson’s disease. Parkinson’s Disease (PD) is a devastating neurodegenerative disorder with a growing impact worldwide.

Though previous studies have found that psilocybin may be helpful for people with depression and anxiety, all of these studies have excluded patients with PD or any other neurodegenerative disorder. TrPR aims to fill the gap of critical information regarding this treatment.

If successful, this project will lay the groundwork for a larger randomized placebo-controlled study of psilocybin therapy for treating PD-associated depression and anxiety. Participants who meet the criteria will be administered both a low dose and a high dose of psilocybin.

To learn more about joining this study or about the work TrPR is doing, visit https://psychedelics.ucsf.edu/pdp!

02/20/2022

Jacob Aday, a post-doctoral researcher at TrPR, has published a new article evaluating the evidence for “comedowns” associated with M**A through an open-label study! The study found that previous research on recreational M**A users was highly confounded by external variables.

When the drug was administered in a clinical context, there was no evidence of affect drop. Check out the article:
“Debunking the myth of ‘Blue Mondays’: No evidence of affect drop after taking clinical M**A
Journal of Psychopharmacology”
https://journals.sagepub.com/doi/full/10.1177/02698811211055809

02/15/2022

TrPR has recently launched a blog on our website! We will be publishing new posts regarding our current studies, introduction to therapies, and related topics weekly. Check out the blog at https://psychedelics.ucsf.edu/blog-0.

We have just published our first blog post, titled “10 things to know before your first psychedelic session”. This post is great for anyone who is new to the field of psychedelic therapies, as well as for people who want to learn more about it.

In addition to the blog, TrPR has also opened an Instagram account, @ trpratucsf! Follow TrPR on Instagram for updates about our studies, information about our program and team, and helpful research and infographics. https://www.instagram.com/trpratucsf/

Mass and social media have recently been abuzz with psychedelics - so what are they, exactly? Psychedelics are psychoactive compounds that can induce an altered sense of consciousness and self, including powerful hallucinations (hence their classification as ‘hallucinogens’) and altered percepti...

12/31/2021

We are excited to announce our USONA study, a Randomized Clinical Trial of Psilocybin for Depression! The purpose of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for major depressive disorder compared to an active placebo.

Eighty participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder will be eligible for this study. Participants will be stratified by study site and randomized with a 1-to-1 allocation to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin, an active placebo.

Participants must be located within the Bay Area for the duration of the study. To be considered for the study, please fill out this pre-screen survey: https://ucsf.co1.qualtrics.com/jfe/form/SV_3wx6TpZ9rfwNnka.

Qualtrics makes sophisticated research simple and empowers users to capture customer, product, brand & employee experience insights in one place.

12/24/2021

This November, TrPR’s Zachary Skiles organized the Veterans + Families Forum in New York City with every VA researcher in the country who is engaged in psychedelic research with veterans. The forum investigated the potential of therapies that use M**A, psilocybin, ibogaine, and ayahuasca to change the lives of veterans that struggle with mental health.

Zach co-hosted the event with TrPR alumni Chris Stauffer, VA staff from New York and Texas, co-founders of Reconsider (creators of the documentary Fantastic Fungi), and Horizons (organizers of psychedelic research). Reconsider and Horizon also produced a feature-length documentary on psychedelics in the veteran community, which Zach is featured in. Check it out at https://vimeo.com/646708536!

This is "Recap: Veterans + Families Forum (November 10, 2021)" by Reconsider on Vimeo, the home for high quality videos and the people who love them.

12/24/2021

TrPR is excited to announce our recent publication led by Dr. Leehe Peled-Avron and Dr. Josh Woolley, Understanding others through observed touch: neural correlates, developmental aspects, and psychopathology. Check out the study at https://authors.elsevier.com/a/1e2br8MqMif400!

Touch is an essential part of social interactions in humans. When we see others giving and receiving social touch, we convert the sight of touch between others into an internal representation of touch upon ourselves and recognize what the other person is feeling. Nevertheless, the mechanisms through which this process occurs are just beginning to be elucidated. Here, we review the neural correlates that underpin observed touch perception.

Several studies indicate that activation in somatosensory cortices enables simulation of the observed touch on the self and activation in insula, TPJ and STG enables the understanding of the other person's emotional and physical experience. The ability to simulate others’ sensory experiences with touch seems to develop during the first year of life. Infants’ brain registers correspondence between the infant's own body and the bodies of others which points to early socio-emotional development.

Different processing patterns of observed social touch are seen in psychopathologies: people with ASD avoid it, in psychopathy, there is no motivation for social touch, and in schizophrenia, it is blurred between self and other. Future research would benefit from exploring different ages and further deepen our understanding of the neural correlates of observed social touch in psychopathologies to aid in forming new forms of therapies that would enhance social functioning in psychiatric conditions.

Touch is an essential and powerful part of social interactions in humans. It is used to convey feelings and thoughts and aids in forming and maintaini…

12/13/2021

Last month, TrPR’s Dr. David Gard (https://merl.sfsu.edu/merl/david-e-gard-phd) published “Could Psilocybin Be Helpful in Bipolar Depression? Is it Safe?” on Crest.BD. Read the full article at https://www.crestbd.ca/2021/11/18/psilocybin-bipolar-depression/

The article covers psilocybin, a breakthrough treatment of depression, and analyzes past findings to highlight the necessity for more research. In fact, TrPR is currently developing a study to test the effectiveness of psilocybin in depression in bipolar 2 disorder: https://clinicaltrials.gov/ct2/show/NCT05065294

Psilocybin Therapy for Depression in Bipolar II Disorder - Full Text View.

12/12/2021

TrPR’s Zach Skiles was featured in The Microdose, a newsletter at UC Berkeley’s Center for the Science of Psychedelics. The article covers Zach’s journey into clinical psychology and his efforts to make psychedelic therapies available to other veterans.

As a veteran who participated in a residential treatment program after returning to the United States, Zach Skiles has personal knowledge about the veteran experience. He believes this insight led him to pursue psychology, which allows him to assist other veterans.

Zach discusses how psychedelic therapy can allow veterans to process their experiences in a variety of new ways that offer somatic, cathartic & regulatory benefits, in addition to cognitive flexibility. Simultaneous experiences occur in a single psychedelic session.

In the article, Zach recounts how he has personally helped 90 US Special Forces veterans in Mexico using psychedelic therapies and group discussions. He emphasizes how important it is for these therapies to become regulated in the United States.

Read about these topics in full detail by checking out The Microdose’s article!

When Zach Skiles was 18, he joined the Marines. Now, Skiles is a clinical psychologist and a postdoctoral researcher working with the University of California at San Francisco’s Translational Psychedelic Research Program (TrPR), and one of many veterans helping connect fellow veterans with psyched...