How psychedelics change your mind – and your brain
- Mirela Baneva
- 2 days ago
- 6 min read
In the realm of psychedelic research, where potential participants are either flooded with difficult to grasp information or are not being presented with some of the key considerations at all, it is of utmost importance to be aware of how psychedelics alter our minds through our biology, and how long those effects could last.
Where do we even begin?
Classical psychedelics (usually referred to as simply “psychedelics”) are a group of psychoactive drugs, meaning they possess the ability to deeply alter our perception, mood, thought patterns, and even personality. Some of these substances are found in nature, like mescaline, which comes from certain cacti, and psilocybin, which comes from mushrooms; while others like LSD and DMT are synthetic in origin. The mind-altering effects of these compounds are precisely what has made them so intriguing, both in ancient times, where psychedelics were mainly used for spiritual rituals and ceremonies, and in the modern age, where their use has been the center of controversy and debate. While the media spotlight often ascribes almost “magical” properties to psychedelics, by understanding the biological basis of their action, we can explain not only the basic mechanism by which psychedelics exert their effects on the human mind but also offer realistic explanations of how psychedelics can make long-lasting changes in people’s lives. However, understanding these scientific principles can be intimidating and overwhelming. When the science is not always easy to decipher, how aware can we be of the prolonged effects of psychedelics and do these effects ultimately interfere with our ability to make good decisions and give consent in the context of research or therapy?
What do psychedelics do to the brain?
Before we can tackle the neuroethics of psychedelics, we need to understand the reality of how psychedelics work. Even though sometimes they are still advertised as such, psychedelics are not magical compounds that just enter our brains and turn them upside down. So how exactly do they exert their effects on perception?
The serotonergic system
After ingestion, classical psychedelics cross the blood–brain barrier (the security barrier that protects our brains from harmful substances and pathogens) and enter the brain, where their first step is to shake hands with the serotonin receptors on the outsides of brain cells (neurons). Serotonin is a molecule used to transmit messages between neurons (also called a neurotransmitter) and is known to regulate mood, sleep, appetite, digestion, and other vital functions. The way serotonin works in the brain is by binding to specialised receptors on the cell receiving the message. Similar to how a key perfectly enters a lock and opens a door, serotonin binds to its receptor, which triggers a cascade down a molecular pathway that further transmits the message. Sometimes, though, even an imperfect replica of the key can still open the door. In the same fashion, the psychedelic molecules resemble serotonin just enough to be able to fit in the lock and bind to the serotonin receptor.
So, does that mean that psychedelics have the same effect on the brain as serotonin? Here the key and lock metaphor becomes redundant, because to the joy of neuroscientists everywhere, the brain is more complicated than most man-made systems. Receptors can still tell the difference, when similar but inherently different compounds bind to them (a phenomenon called biased agonism). Therefore, when serotonin molecules and psychedelics bind to the same serotonin receptors, the receptors activate different response pathways. The different responses elicited by psychedelic compounds lead to the profound effects on perception and behaviour seen with psychedelic use.
Differences in gene regulation?
Before we arrive at said “profound effects”, there are a couple more intermediate steps. For a long-lasting effect to be established in the brain, genes are always involved and that is also the case in the psychedelic story. When the psychedelic molecules meet the serotonin receptors, a different communication pathway is used, which leads to the activation of early–acting genes. These genes are called “early”, because they are triggered within minutes of the initial handshake with the serotonin receptors. What these genes do is simply pass the ball onto other genes that are involved in plasticity. What does that mean in this context? Plasticity refers to how connections between neurons become stronger or weaker over time–which is the basis for long term changes in behaviour. Using this mechanism, psychedelics appear to promote plasticity (and as a result, behavioral changes) by altering which genes are turned on in certain brain areas.
From the initial binding to serotonin receptors through increases in brain plasticity, the altered expression of genes in activated neurons likely underlies the long-term changes observed following a treatment with psychedelics. Changes can include the dissolving of detrimental thought patterns in mental health ailments like depression, which usually leads to better personal outcomes. Next, we will see, however, that negative changes can be perpetuated using the same mechanism.
Long-lasting effects
The administration of classical psychedelics can result in behavioral and personality changes that last from weeks to even years after initial exposure. This aspect is especially notable, since these traits are normally regarded as stable, and therefore unchanging, throughout adulthood. The relevance of this change-inducing quality of psychedelics becomes even greater when we talk about mental health disorders like depression and anxiety, where the improvement of symptoms after psychedelic use has been documented and has encouraged interest in psychedelic-assistedpsychotherapy.
But how long do positive outcomes actually last? One study evaluated individuals after a single dose of LSD (either with or without supervision from a psychotherapist) and found that positive personality changes can persist for as long as 10 years after the use of the psychedelic. In a more recent follow-up study, increased mindfulness and improved psychosocial functioning were shown to last 3-4 months after a single administration of psilocybin. Even though scientific papers and the media usually highlight the positive effects, acute negative experiences under the influence of psychedelics are not rare. In a study focused on rats that were repeatedly given LSD, it was observed that the rats changed their social behaviours to hyperactive and irritable, and decreased desire for their regular food. Some of the negative behaviours like hyperactivity persisted almost unchanged even after the rats were taken off the LSD. This indicated potential permanent changes in brain chemistry and a shift in gene expression from a normal to a pathological state.
Even though animal models are useful to observe changes in the brain caused by exposure to psychedelic substances, human complexity cannot be reduced to that of a lab rat. In humans, and more specifically healthy adult volunteers, one notable study reported 40% prevalence of moderate to severe anxiety, panic or distress after the administration of a high dose of psilocybin. Such instances of psychological discomfort are commonly referred to as “bad trips” and are frequently accompanied by changes in thinking and behavior.
Even though these ‘bad trips’ are often taken lightly and believed to be relatively short in duration, this is not always the case. For example, one study focused on people who reported sustained negative effects that lasted a few days after psychedelic treatment. These individuals reported negative experiences such as anxiety, panic, intrusive thoughts, depressive symptoms, and general psychological distress. Ultimately, the study supported the real possibility that worsening mental health can occur as a consequence of psychedelic-use.
Take-home messages
Psychedelics act on the serotonergic system in the brain to trigger alternative pathways of gene expression linked to neural plasticity. These changes are thought to underlie the long-term effects on behavior associated with psychedelic use. Crucially, however, the same biological mechanisms that support the long-lasting therapeutic benefits, can also contribute to the prolonging of potential adverse effects.
The possibility of lasting negative effects is therefore one of the key issues that requires careful ethical evaluation before patients can safely and meaningfully participate in psychedelic-assisted treatments, or volunteers can take part in clinical trials. But potential pitfalls don’t end there.
In the newest season of our podcast, premiering on June 1st, 2026, we will be investigating the neuroethical challenges that accompany the study and use of psychedelics in recreational and therapeutic settings. To coincide with this new podcast season, we will also be featuring several blog articles addressing psychedelics and the ethical concerns we must be aware of prior to advocating for their use in healthcare. In this first article, Neuroethics Today assistant editor Mirela Baneva will help us to establish a foundational knowledge by introducing us to psychedelics and how they work to change our brains, and thus, our behaviors. Don't forget to follow us on LinkedIn so you never miss an update!
Comments