The Bay Area holds a long-running reputation as a hub of recreational psychedelic use. The rise of the counterculture movement in the 1960s was largely based out of the Haight-Ashbury district of San Francisco, with popularization of experimentation with consciousness-expanding substances leading to the inception of new genres of rock music, creative movements in the arts, and increased interests in communal living and alternative lifestyles. The expanding use of these so-called “psychedelics,” such as magic mushrooms (psilocybin) and acid (LSD), created a rift in society, with some condemning the dangers of unpredictable behaviors while on these substances, and others praising the lasting aftereffects of peace. Years of legislation criminalizing these substances prevented scientific research into the clearly profound effects of these substances on the human mind.

The presence of psychedelics is still evident in the modern Bay Area, with Silicon Valley techies taking miniscule doses of these drugs on a regular basis to increase job performance and creativity (called “microdosing”) and legislators decriminalizing the possession of psilocybin and other psychedelic drugs in major cities such as Oakland, Berkeley, and Santa Cruz. Concomitantly, increasing reports of mental health benefits from those receiving psychedelic-assisted therapy have led to some major insurance companies providing cost-assistance for patients suffering from emotional distress that have failed more traditional forms of talk therapy and psychiatric medication. Additionally, the biopharmaceutical industry is growing to meet this unmet need, and an entire legal psychedelic pharmaceutical market is arising. So, after many years of criminalization, there is a resurgence of academic and public interest in these substances.

In September 2020, UC Berkeley opened a research center, the Berkeley Center for the Science of Psychedelics (BCSP), that funds biological, anthropological, psychological, and policy research to provide a holistic understanding of how psychedelics influence the body, mind, and society. One of the first centers of its kind, the BCSP stands ahead of the curve by offering basic science research as well as educational and training tools for integration of the acquired knowledge into society. The center also offers a training program for mental health therapists to offer psychedelic assisted sessions, in addition to several public education methods, such as a podcast, Altered States, and a newsletter, The Microdose. A free course is available for the public to audit based on the popular “Drugs and the Brain” undergraduate neuroscience course taught by campus psychedelic science expert, Professor David Presti.

In the four years since its inception, the BCSP has gained national attention and conducted one of the first large-scale studies of public opinion on psychedelics. The 2023 UC Berkeley Psychedelics survey asked people from all over the United States a host of questions about their knowledge of psychedelics and found that, regardless of their level of personal relationship with psychedelics, 78 percent supported making it easier to research psychedelics. Imran Khan, former executive director of the BCSP and current informal advisor, further summarizes the results: “Most people who’d recently heard something about [psychedelics] were associating them with something to do with mental health.” The overwhelming majority of voters, he continues, “were interested in more research” and “more regulated access to psychedelics.”

Increasing interest in psychedelics is already changing the direction of neuroscience and mental health research, and UC Berkeley’s research efforts are evolving in tandem. At the moment, there seem to be more questions than answers about how psychedelics impact the human experience. Imran highlights that “one of the biggest things [psychedelics] reveal is how little we know rather than how much we know.”

What are psychedelics?

Psychoactive substances are chemicals that, when ingested, can alter bodily function via interaction with the nervous system. Many of these come directly from or are chemically related to naturally occurring compounds in plants or fungi. Psychedelics (from the Greek psykhē for “mind/spirit” and dēloun for “show/manifest”) are a subcategory of psychoactive drugs that profoundly change the state of the mind via alterations in sensory processing, resulting in an altered state of consciousness.

Compounds such as psilocybin, LSD, mescaline, and ayahuasca are “classical” psychedelics because they all mimic the normal activity of one neurochemical naturally synthesized in the brain: serotonin. Serotonin modulates how neurons communicate with one another and has been a target of psychiatric research due to its known association with consciousness and mental health conditions. Because of their structural similarity to serotonin, classical psychedelics directly activate serotonin receptors, which can result in effects such as increased neuronal connections and alterations to thought patterns. This group of psychedelics can induce sensory distortions, mystical or spiritual experiences, and dissolution of the ego, one’s sense of self. Additionally, classical psychedelics hold high therapeutic potential because they reduce psychological defense mechanisms and have low abuse potential and toxicity.

Renewal of the self

In some cultures, it is common to conduct spiritual renewal ceremonies that include the use of psychedelics to expand consciousness, symbolize an identity shift, or offer a ceremonial cleansing of one’s old ways. Even before these plant-inspired medicines of the self were popularized and explored in modern science, humans across history have used psychedelics to alter the state of the nervous system. Another term for psychedelics is “entheogen,” which means “revealing god within,” indicating the profound quality of these molecules to stimulate experiences of interconnectedness within oneself and the universe.

Reports of vivid visual experiences on ayahuasca, a serotonin-receptor activating ceremonial psychedelic beverage originally used in shamanic tribes in the Amazon, involve common themes of seeing tunnels, “beings of light,” or spiritual guides, leaving the user with revelations of internal wisdom. Large doses of psychedelics can induce dissociative, dreamlike visions that depict ongoings in one’s internal world, or subconscious. Psychedelics seem to “lift the veil” between the conscious mind and its unconscious stored material, allowing one to observe their own thought patterns with renewed understanding. Strong hallucinogenic experiences can prompt reevaluation of one’s own beliefs and mental blocks that could take years of traditional psychotherapy or meditative introspection to overcome. The resulting personal identity transformation can balance one’s sense of self and heighten awareness, also termed a spiritual awakening.

Although there are general trends in sensory experiences under each classical psychedelic, the meanings of the visuals are extremely specific to one’s own mind. Psychedelics are considered “nonspecific amplifiers,” meaning that the experiences or “trips” themselves are individualized and context-dependent, and the same substance will not induce a specific belief system change in all people. Some trips could be terror-inducing, and others peace-inducing, depending on the state of the mind at the time of ingestion. Context and community are crucial to the outcome of the experience. In a supportive environment, such as a traditional medicine ceremony or mediated therapy, psychedelics can stimulate personal epiphanies, sometimes in visual form.

Opening the doors of perception

A large focus of the BCSP is to understand the neurobiological mechanisms underlying successful outcomes of psychedelic therapy in hopes of creating eventual streamlined treatment options. One of the most exciting developments of the BCSP was approval for campus researchers to conduct testing on human subjects under the influence of psychedelics. Vision Science and Neuroscience Professor Michael Silver’s lab does so by exploring how the human visual system operates differently when exposed to psilocybin.

Dr. Sean Noah, a postdoctoral researcher conducting neuroimaging studies in the Silver lab, comments on his line of research: “Psychedelics, in general, are very compelling tools for studying vision and how the brain creates our visual perception because they can so profoundly affect vision.” He continues, “There’s lots of different visual effects that are characteristic of psychedelics or hallmarks of psychedelics, like warping of textures and surfaces, drifting and illusory motion, and color changing.” The well-studied field of vision science is a great starting place to introduce questions about how psychedelic molecules function. Interestingly, one type of serotonin receptor is highly expressed in the layers of the brain responsible for visual processing, suggesting a potential direct target of classical psychedelics.

Vision researchers understand that visual perception, or the image of the world constructed by the brain, isn’t all that it appears to be. Most of us assume that our eyes are like cameras, taking in raw data about the world around us and creating a picture in our brains. As it turns out, Dr. Noah explains, the brain does a significant amount of processing to create visual perception from the “very distorted and noisy” signal collected by the retina in the back of the eye. Our brain “fills in” what it predicts should be there based on past experiences, and what results is a consistent and continuous visual percept of the world.

Describing the organization of the brain’s visual system, Dr. Noah explains, “We think of the [visual] cortex as being hierarchically organized, and moreover, we think that there are reciprocal connections between the stages of this hierarchy.” Part of the work in the Silver lab involves studying the specifics of how psychedelics change signal transmission along this organization, and Dr. Noah’s experiments are centered around studying the tradeoff between “top-down” and “bottom-up” processing. He clarifies the details of this theory: “Predictive processing theory proposes that the top-down signals in the brain are what are sending the predictions from the model to lower-level visual areas to try to compare with the retinal input to see how accurate the model is and then update it if necessary. And the feedforward or the bottom-up signals are sending prediction errors where the predictions from the model are compared against the retinal inputs and any discrepancy is propagated forward to update the model.” So, the brain creates generalized mental maps of the environment, and the eyes scan and compute if anything is different from the model of our surroundings pre-generated in the mind. Dr. Noah summarizes, “So what we perceive is actually an inferred model of how the world is structured.” Psilocybin is hypothesized to alter our normal mode of model testing.

To conduct these human studies, research subjects arrive on campus and enter a functional magnetic resonance imaging (fMRI) machine while under the influence of psilocybin. They are asked to perform a series of standardized visual tasks, such as distinguishing between optical illusions. The subjects’ brain scans and task performance indicate how specific qualities of their perceptual abilities are impacted. fMRI scans act as an indirect measure of brain activity, indicating where oxygen is being used by neural tissue, and allow researchers to deduce what regions of the visual cortex and associative areas are active during certain tasks. Regarding the novelty of the study paradigm, Dr. Noah remarks, “It’s pretty unusual for people studying psychedelics with neuroimaging to combine psychedelic administration with performance of a visual task.” He also highlights that “the strength of our study is that we’re using a well-controlled visual task design… to help explain how psychedelics have their perceptual effects in the first place.”

Psychedelics are thought to change visual perception by shifting the brain’s processing away from being heavily biased by visual priors—past visual experiences and assumptions about what to expect—and toward one more nuanced by raw visual data. In essence, they are thought to work by re-weighting how much our internal framework and belief systems influence our literal worldview. Furthermore, the predictive processing theory and altered tradeoff between top-down and bottom-up processing may be responsible for some of the therapeutic effects outside of vision. Termed by BCSP collaborator at UCSF, Professor Robin Carhart-Harris, the relaxed beliefs under psychedelics (REBUS) theory—which is an extension of predictive processing theory—posits that psychedelics reduce the influence of prior experiences in generating our conscious experience. As studies like the Silver lab’s gather more information on how visual processing shifts under the influence of psychedelics, subsequent BCSP projects will expand to other less-understood areas of the brain, such as those associated with one’s sense of self. The end goal is to understand how psychedelic therapy is influential in changing one’s personal narrative. For example, patients often report increased self-esteem after psychedelic therapy. According to REBUS theory, this could be due to both decreased influence of prior self-narratives and increased input from direct sensory processing, resulting in liberation from past beliefs. Patients can even de-identify with their past mental health conditions. Imran comments on this phenomenon in the context of emotional priors: “Maybe one of the things that psychedelics are doing is dampening or weakening the influence of those priors that allows you to reinterpret things like memories in a different way.”

The key to recovery from post-traumatic stress disorder?

Nightmares, traumatic memory replay, depression, and anxiety are characteristic of post-traumatic stress disorder (PTSD), and selective serotonin reuptake inhibitors, or SSRIs, are typically the first-line psychiatric treatment for PTSD-associated anxiety and depression. However, psychedelic-assisted sessions have also been found to alleviate symptoms for many patients. Researchers suspect that psychedelics may offer a longer-term alternative to daily SSRI use, due to their profound impact on the brain’s serotonin network.

Neuroplasticity, the adaptive restructuring of neural connections with experience, is a focus of current behavioral and molecular psychedelic research. The serotonin molecule modulates neuroplasticity, promoting new connections between cells. Psilocybin magnifies this role of serotonin on a larger scale. Dr. MeeJung Ko, a postdoctoral researcher in the Integrative Biology department, enthusiastically explains that recent scientific literature provides evidence that psychedelics can “rewire brain circuits, which is very fascinating because no drugs so far have shown that extensive capacity in terms of changing the holistic aspect of the brain.” Dr. Ko’s experiments in the Kaufer lab merge the field of PTSD research with psychedelics to understand how serotonin receptor-activating molecules like psilocybin influence neuroplasticity, and how this can explain mental health symptom improvement.

Psychedelic research in the realm of behavioral neuroscience has generally focused on psilocybin’s effects on the prefrontal cortex, the brain area responsible for meta-cognition, since it contains the highest density of serotonin receptors. Dr. Ko’s work focuses on a brain area connected to the prefrontal cortex that also expresses serotonin receptors, the hippocampus. The hippocampus is housed deeper into the brain, under the cortex, and is involved “in different types of learning, like emotional learning or reward learning,” as Dr. Ko describes, both of which are perturbed in clinical cases of PTSD. It is crucial to understand how the hippocampus may respond to psilocybin, as patients with PTSD often experience volume loss in this region, possibly accounting for flashbacks and fear-associated traumatic memories. Whether or not psilocybin alters the function and structure of cell types in the hippocampus is unknown.

Previous work in the Kaufer lab found an association between acute stress conditions and abnormally elevated myelin levels and increased number of oligodendrocytes, a type of glia or non-neuronal cell, in rat hippocampus. In her work, Dr. Ko discovered that mouse models of PTSD demonstrate decreased anxiety behaviors after psilocybin exposure. Bridging these two findings, she is currently examining whether those psychedelic-associated behavioral changes are correlated with changes in tissue-level activity in oligodendrocytes. Oligodendrocytes are required for healthy brain function because they generate the myelin that insulates axons (cell communication “wires” in the brain), which allows for higher-speed neuronal communication. Abnormal elevations in oligodendrocyte activity, and in turn increased myelin, may lead to over-excitation of these neuronal networks and give rise to symptoms related to anxiety and PTSD. However, there is currently no definitive link as glia have not been of major interest in neuroscience research until recent years. Dr. Ko comments, “A lot of people still think that glia are just supporting cells, but [we now] know that they are beyond supporting, and they actually have a critical role in the brain.” Dr. Ko’s studies aim to reveal how the brain responds to psychedelics at a regional and molecular level by illuminating what functions oligodendrocytes play within memory pathways in anxiety and PTSD, and how these roles may be altered by psychedelics.

Dr. Ko, driven by the translational use of psychedelics, asks, “can we use those mechanisms [currently being elucidated] to develop next-generation therapeutics?” She mentions how early we are in discovering the basic science of psychedelics and the broader impacts of her research: “Right now we’re still trying to understand how it works, and I think it’s important because that could also potentially help us understand what the mechanism is for […] adverse effects of psychedelics.” Dr. Ko hopes to apply her work understanding how psychedelics affect the brain to create effective and specific psychedelic treatments for psychiatric disorders. Case reports indicate that simultaneous SSRI use or history of psychosis can greatly increase the likelihood of negative outcomes from using psychedelics, but not how or why that is the case. Imran also emphasizes that “psychedelics are in some ways like any other drug, in that they have potential benefits and upsides and they also have potential risks and downsides.” He continues, “Nowadays we’re lucky that there is much more information about both those risks and potential benefits available.” Minimizing risk factors is an important goal for both researchers envisioning how basic research might apply to eventual pharmaceutical applications, and for individuals when considering personal use for relief of mental health suffering. If you are personally interested in undergoing psychedelic therapy, it is essential to do so with a trained professional who can understand how your mind is operating differently in a labile state. Psilocybin-induced neuroplasticity may reopen flexible brain states similar to neurodevelopmental windows in childhood, allowing for new brain circuits more suited to current psychological needs to form. Whether in the case of visual perception or anxiety, psychedelics might quite literally be “opening the mind” on a neural level, enabling the subject to create new synaptic connections and transform their perception.

Looking ahead

Psychedelics have long enraptured thinkers interested in philosophy of mind (the study of consciousness), with several famous philosophers and scientists reporting regular use of psychoactive substances to explore the extent of their own minds, leading to discoveries that changed the course of human knowledge (such as Francis Crick, who reportedly envisioned the double-helix structure of DNA while under the effects of LSD). Perhaps increasing research and community around psychedelics in modern culture will release untapped potential innovation within society as a whole, as well as encourage normalization of individual self-renewal.

We are meant to metamorphosize across our lives with our identities constantly fluctuating in society as we age from children to adults to elders. By nature, we cannot stay the same, but often the mind struggles to accept change both in our environment and within ourselves. Sometimes behavioral and thought patterns that protected us in the past no longer help us and instead cause us pain. Many times, we unconsciously choose to stay stuck because of fear of greater pain, but a spark of hope is all we need. Beginning psychedelic therapy may feel like a last resort to some, but it takes immense bravery to take the leap into facing the unknown within for the possibility of existing in a future mental state with more ease and peace.