Third Wave write…
Over the last 15 years, the hallucinogenic drug lysergic acid diethylamide, or LSD, has reemerged in public conversation as a powerful healing tool, a productivity and creativity catalyst, and a vehicle for collective spiritual transformation.
This article is your comprehensive introduction to the neurological, perceptual, and psychological effects of LSD, and it aims to quell the LSD-makes-you-jump-out-of-a-window anxiety that has permeated the collective consciousness since the seventies. Here, we explore the true risks to LSD users (spoiler: no window-jumping involved) and how to mitigate them. Additionally, while the field of psychedelic science is still in its relative infancy, we review some data on LSD’s long-term effects.
GENERAL SHORT-TERM EFFECTS OF LSD
In the context of LSD’s use in psychotherapy and psychiatry, LSD does not really fit the standard psychopharmacology label of a “drug” with “effects”. Unlike antidepressants, for example, LSD is a facilitator of an experience.
The details of that experience depend heavily on various factors, including the dose of LSD, the environment the LSD is taken in, the psychological state of the person taking it, and the cosmological and theoretical background of the guide or therapist holding the space. These factors are summarized as set and setting.
Because of the wide diversity of set and setting, no two LSD “trips” are alike. Consumed on a piece of blotter paper, gelatin tabs, or in sugar cubes, you might have visual hallucinations, or experience synesthesia—the blending of the senses—as you hear the color purple or see the sound of music. At higher doses (200-500 mcg), you might experience your own birth, travel through time, or dissolve into oneness with the entire universe.
LSD journeys can feel ecstatic and liberating, but they can also be challenging and uncomfortable. That’s why it’s always a good idea to prepare well and have a guide present to keep yourself safe and mitigate “bad trips” or experiences.
Physical side effects can include fluctuating blood pressure and body temperature, increased heart rate, dry mouth, and a loss of appetite, yet these are usually manageable and pass quickly.
But what is happening in the brain during all of this? How can such powerful experiences such as “dissolving into oneness” occur as a result of ingesting 0.0002 of a gram of one little molecule?
NEUROPSYCHOPHARMACOLOGY OF LSD
Effects on the neurotransmitter serotonin
LSD is a “classic” psychedelic, which means, like the hallucinogens DMT, psilocybin (magic mushrooms), peyote, and ayahuasca, its primary mechanism of action is to bind to the 5-HT2A serotonin receptor.
Activation of these serotonin receptors is thought to produce the “psychedelic”, subjective effects of LSD, because when researchers give participants LSD but block the 5-HT2A receptors, the participants don’t experience any subjective effects.
What’s most interesting about LSD is that not only does it bind to the 5-HT2A receptor more strongly than any of the other classic psychedelics, it binds more strongly than serotonin itself. Part of the receptor folds over the LSD molecule like a lid, keeping it in place—possibly explaining the long duration of LSD experiences (8-12 hrs), as well as its strong binding affinity.
In addition, LSD’s transformational capacity makes sense when you consider that the 5-HT2A receptor is expressed at high levels in the prefrontal cortex (PFC). The PFC is the most recently evolved part of the brain, responsible for higher order functioning like complex cognitive behavior and personality expression. So the fact that LSD has such a powerful neurological presence in this area sheds light on why journeyers can come out of an LSD experience with new insight and a shift in who they think they are.
Effects on dopamine
Although LSD does directly activate several dopamine receptors in rats, the exact pharmacology in humans is unclear. However, it is known that LSD does not increase the amount of dopamine in the human brain, which makes it (and the other classic psychedelic drugs) physiologically non-addictive.
Effects on the central nervous system and nerve pathways
Before going into how LSD affects the brain on a systems level, it will be helpful to understand a few things first.
Right now, life probably feels normal. You’re reading these words, you might feel the handle of a coffee mug in your hand, and you might be dimly aware of a sense of “you” processing everything.
But how can this be? Light from the sun or the ceiling is bouncing like crazy on every surface. You have trillions of bacteria churning away your lunch in your digestive system. Receptors all over your body are sending electrical signals to your 86 billion neurons about your sitting position, the movement of your pancreas, and the feelings of your memories. How are you not rolling haphazardly on the floor exploding with information?
The answer is: you’re hallucinating.
Everyday waking consciousness is the first hallucinogen, because our brains synthesize millions of bits of random information every second into a cohesive picture we call “reality”. That synthesis is primarily performed by an interconnected group of brain regions called the Default Mode Network (DMN), which acts like an orchestra conductor for your brain, managing the furiously complex electrical signaling in the brain so you can experience an orderly, predictable reality.
So where does LSD fit into all of this? Put simply, LSD kicks the orchestra conductor off the stage. In other words, it quiets down signaling in the DMN, allowing regions of your brain that don’t normally signal to each other to leap into new electrical harmonies. This is why “LSD changed everything I thought I knew about the world” is such a common response to a journey, because it dramatically disrupts the network in your brain responsible for creating your normal reality.
In addition, the DMN is often referred to as the “me network”, because the most basic component of everyday reality it creates is a sense of “me” experiencing it. When you take LSD, the quieting down of the DMN can lead to ego-dissolution, where that sense of “me” dissolves and a more primal, interconnected consciousness is revealed.
For a scientific breakdown of the nature of that primal consciousness, check out neuroscientist Robin Carhart-Harris’s “Entropic Brain” hypothesis. For a more spiritual account, check out LSD and the Mind of the Universe by philosopher Christopher Bach.
Effects on anxiety
Since LSD can radically shift the hallucination of reality that we’re used to, it’s understandable that some anxiety is often a part of the experience. This is why preparation is key: an active practice in surrender through meditation or Holotropic Breathwork and a trained guide can help significantly in mitigating any anxiety during a journey.
In fact, one seminal study actually used LSD to help terminally ill patients cope with their debilitating anxiety surrounding their impending passing. However, this study was small and contained no placebo group, so further research is still needed.
DOES LSD DAMAGE YOUR BRAIN?
But LSD seems so intense, surely there must be some life-threatening damage to the brain, right?
Short answer: nope.
After LSD wears off, the DMN returns to its normal functioning, and LSD has been shown to be physiologically non-toxic. If anything, LSD helps your brain—it promotes neural plasticity, which means it increases the amount of synaptic connections between neurons as well as promoting the growth of new neurons.
LSD RISKS & WHEN NOT TO TAKE LSD
However, there are risks associated with LSD.
First and foremost, LSD is still illegal in every country, with the only quasi-exception being Portugal. Read our LSD legality blog post to learn about the specifics concerning decriminalization in some countries.
Then there’s the matter of purity. As is the case with most synthetic compounds, it’s hard to tell what you have by just looking at it, so practice responsible drug use and test your LSD before using it.
For example, a drug called DOI is frequently sold as LSD. DOI is much more intense. It can last for 16 to 30+ hours, and effects of the drug include trouble sleeping, pronounced visual effects, and a heavy body load. Having a DOI experience when you were expecting an LSD experience can be unpleasant, so again, always make sure testing is part of your substance use.
Once you’ve accounted for legality and purity, the remaining risks are psychological and spiritual.
If you have a family history of psychosis or schizophrenia, you should not take LSD, because there is a risk of triggering a psychotic episode or developing severe depression. If you have a severe mental illness—like depression, panic attacks, or substance abuse—you should absolutely journey with a guide or therapist who will be able to create a container of healing and integration. And in general, for anyone experimenting with hallucinogens or dissociative drugs, you should make sure to have some sort of support—an online integration group, a close friend, or even literature about the psychedelic experience—to ground your experiences in everyday life and prevent spiritual or existential emergencies.
For folks without a family history of psychosis or schizophrenia who still wonder if there are cases when they should not take LSD, it might be helpful to return to the idea that we hallucinate our everyday reality.
We’ve established that, when taken in a proper setting with a guide, LSD can be very safe. Your brain returns to DMN functionality after the experience, there is little risk of addiction, and proper integration can help ensure minimal psychological suffering or other adverse effects.
So the best barometer of whether or not you should take LSD is one question: Am I prepared to, in some capacity, let go of what I currently think is true about myself, the world, and my relationship to it?
Although Swiss chemist Albert Hofmann synthesized LSD all the way back in 1938, science doesn’t yet definitively know the long-term effects of LSD, only because there have not been many longitudinal studies on its long-term effects. However, we do know some things.
On the negative side, a condition called hallucinogen persisting perception disorder (HPPD) can occur. HPPD is characterized by a continual presence of sensory disturbances, most often visual, sometimes continuing for months or years following psychedelic use. This is different from flashbacks. HPPD is rare and most likely a result of drug abuse, for it has not been seen in psychotherapy settings.
On the positive side, there is one recent study that found no correlation between use of LSD and mental health problems or suicidal behavior. In addition, although the psychiatry studies from the ’50s and ’60s don’t meet current standards for the validity of scientific research because of a lack of placebo groups, many found no lasting brain damage in participants. This would make sense considering that, as we learned above, LSD doesn’t harm the brain in the first place.
But while Western science moves to legitimize the safety of psychedelics in future clinical trials, we should keep in mind that intense serotonergic psychedelics have been around for a long time. Psilocybin mushrooms and ayahuasca, which both act on the 5-HT2A receptor and quiet down the DMN like LSD, have been used safely and with transformative intent in indigenous cultures for thousands of years.
Of course, these medicines are of the earth and while LSD is derived from the ergot fungus, it was made in a lab, so the comparison is not a completely viable indication of LSD’s long-term safety profile.
Regardless, LSD is on the path to revolutionize psychiatry, mental healthcare, and how we as a people see ourselves. But with great power comes great responsibility. If the last half-century of illegality represented the ashes of LSD’s potential to help people, then we must be responsible, well-informed, and conscientious as the phoenix of psychedelic therapy rises.
Want to learn how psychedelics can help you level up your life and improve well-being, while starting with small doses instead of a full-scale macrodose journey? Try Third Wave’s Microdosing Course. Using the latest research from cutting-edge scientists and doctors, we’ll help you develop a customized, step-by-step process to change habits, enhance creativity, and optimize performance.
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