An intimate look at the subjective effects of LSD and its wide-ranging therapeutic potential
In the 1950s and 60s — the golden age of psychedelic research — many thousands of patients were administered LSD (lysergic acid diethylamide), in conjunction with supportive psychotherapy, for the treatment of a variety of mental disorders, including anxiety, depression, and substance use disorder.
Over a thousand papers were published reporting the results of these studies — the majority of which produced positive therapeutic outcomes.
LSD’s extraordinary psychological properties had a strong influence on psychology and psychiatry in the ‘50s and ‘60s, but mainstream popularity, increasing recreational use, association with the counterculture movement, and media manipulation provoked the drugs being made illegal in the United States in 1968.
Not long after, a war on drugs was declared, and all psychedelics were placed into schedule I of the Controlled Substances Act of 1970 — the most restrictive drug schedule. Manufacture, importation, possession, use, and distribution of psychedelic drugs were regulated. Even scientific investigation of psychedelic substances was outlawed.
The subjective effects of LSD start to take hold approximately 20-60 mins after ingestion and last for 6-12 hours. An LSD-induced psychedelic experience may be characterized by the following psychological effects:
In a 2015 study on the acute subjective effects of LSD administered to healthy people, 50% of participants reported that they could not think of a more pleasurable experience than that which they enjoyed under the influence of 200 micrograms of LSD. This happy, blissful state is dose-dependent and, interestingly, the higher the dose, the more likely people are to report feelings of increased openness, closeness to others, trust, and emotional empathy.
The non-ordinary state of consciousness induced by LSD can also engender the feeling of having an indescribable or “ineffable” mystical experience that has a noetic or revelatory quality. Experiences like this can be profoundly transformative, and so LSD has been used for religious, spiritual, medicinal, and recreational purposes for decades.
LSD can also invoke “Mind at Large” — a concept introduced by author Aldous Huxley to interpret the psychedelic experience. Huxley hypothesized that the human brain filters reality to guard our consciousness against sensory overload. Psychedelics, he said, remove that filter, exposing explorers to the oceanic boundlessness and universal interconnectedness of Mind at Large.
Interestingly, mystical-type experiences have been associated with better therapeutic outcomes in patients with treatment-resistant depression and anxiety.
The physical and physiological effects of LSD are generally considered harmless. There is no evidence to suggest that LSD does any long-term physical damage, nor is there evidence of a fatal overdose ever having occurred.
The physical/physiological effects of LSD may include:
Although LSD does have a very good safety profile, people who meet any of the following criteria are excluded from clinical trials and are strongly advised to refrain from recreational use:
People interested in experimenting with psychedelics, for whatever reason, should understand the heightened risk and potential dangers of uncontrolled use. The likelihood of having a difficult experience or “bad trip” is considerably higher when taking psychedelics in an uncontrolled environment.
Not to mention the possibility of meaningful or cathartic experiences being dismissed as trivial by individuals lacking sufficient understanding of the therapeutic power of psychedelics.
Researchers urge that psychedelics can be profoundly destabilizing if they are not taken in the right context. People should ensure that they are in a good mindset going into the experience and that it will take place in an environment they feel comfortable in — this is typically referred to as “set and setting.”
A good mood and comfortable circumstances are foundational to positive experiences.
Where possible, users should ensure that there is a trusted individual on hand to sit with them throughout their experience to offer reassurance during confusing or scary moments.
Also, the importance of taking the right dose cannot be understated. As the concentration content of psychedelics varies considerably, users are advised to err on the side of caution and start with a low dose.
Before using psychedelics to self medicate mental health issues, one should carefully consider the following reminders:
According to David Nichols, revered medicinal chemist, the discovery of LSD very much catalyzed a neuroscientific revolution. Its powerful psychoactivity even inspired biochemist Betty Twarog to search for and eventually isolate serotonin in the mammalian brain in 1953.
So, what exactly does LSD do in the brain?
A synthetically complex and somewhat complicated molecule, LSD stimulates a whole host of serotonin receptors. Unlike a drug like MDMA, which releases serotonin and inhibits its reuptake, LSD takes the place of serotonin in receptors and directly stimulates the receptors by itself.
A mechanistic study conducted by neuropsychologist Dr. Katrin Preller and colleagues at the University of Zurich indicated that LSD initiates psychedelic effects exclusively via its activation of the 5-HT2A receptor. Study results demonstrated that subjective LSD-induced effects were fully blocked by a 5-HT2A receptor antagonist drug called ketanserin, signifying the central role of this receptor in mediating LSD-induced psychedelic experiences.
When LSD binds to the serotonin receptor, the receptor accommodates itself to the shape and size of the LSD molecule. What happens inside the receptor cell is entirely dependent on the nature of the drug, and so LSD stimulates a very different signaling pattern than serotonin or other psychedelics.
Because the 5-HT2A receptor is open just a small percentage of the time, LSD essentially gets trapped in there for many hours. This is likely what explains LSD’s unique potency and long-lasting effects.
Using a comprehensive placebo-controlled neuroimaging design, researchers in the UK investigated the acute brain effects of LSD in healthy volunteers.
In this study, LSD was found to increase cerebral blood flow in the visual cortex and increase resting-state functional connectivity in the primary visual cortex. These changes were shown to predict the magnitude of visuals experienced by participants.
LSD has also been shown to increase functional connectivity between the default mode network (DMN), an interconnected network of brain regions (that is active when we are at rest and lost ruminative thought), the visual network, the sensorimotor network, and the auditory network. These changes correlated with a profound alteration of consciousness characterized by ego-dissolution — an effect that had also been observed in an earlier study using LSD's classic psychedelic cousin, psilocybin.
A subsequent study conducted by researchers at the University of Basel supported these findings and showed additional connectivity enhancement between distant, usually separated brain regions. These findings suggest that LSD-induced alterations in brain connectivity may be responsible for the induction of the psychedelic experience, ego dissolution, and associated therapeutic effects in distinct mental disorders.
While these insights advance knowledge on the neural correlates of the psychedelic experience, some experts have expressed skepticism regarding the centrality of these specific effects on the human brain. Further imaging studies are needed before any strong conclusions can be drawn.
Now, amid the so-called psychedelic renaissance, LSD is regaining popularity for its medicinal utility as an adjunct to psychotherapy for those struggling with mood disorders — and yielding promising results. The first double-blind, randomized, active placebo-controlled study in the modern era using LSD in patients found that LSD-assisted psychotherapy significantly reduced anxiety in 12 patients with life-threatening diseases.
In addition, biotech company MindMed recently announced the results of their Phase 2 study of LSD for anxiety, which found rapid, long-lasting and significant reductions in anxiety at 16 weeks post-treatment.
It should go without saying, though, that any treatment involving the use of a mind-altering psychedelic drug, is very delicate, and needs to be augmented with supportive practices. If safety protocols are met, then LSD could prove to be an incredibly effective tool in the armamentarium of health professionals.
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