Study finds LSD produces dreamlike states in awake humans by stimulating serotonin receptors

Researchers from the University of Zurich have uncovered more about how the psychedelic drug LSD produces a dreamlike state of consciousness in healthy humans when awake.

LSD produces vivid hallucinatory imagery along with alterations in thought processes related to space, time, causality, and selfhood. The new study suggests that LSD induces these dreamlike states of consciousness by stimulating the serotonin 2A receptor, one of the 14 serotonin receptors in the brain.

“Working as a senior psychiatrist in a depression ward at the Psychiatric University Hospital Zurich, I witness the great suffering and psychosocial burden of depressed patients on a daily basis,” explained the study’s corresponding author, Rainer Kraehenmann. “Current pharmacological and other biological treatment options are limited in terms of both effectiveness and tolerability. Therefore, there is a huge unmet need for innovative, efficacious and well tolerable medication for the treatment of mood and anxiety disorders, especially treatment-resistant depression.”

“Our research has been focusing on research into the therapeutic mechanisms of classic psychedelics (‘mind-revealing’ drugs that activate serotonin 2A receptors in the brain) for years. Our studies have consistently shown that psychedelics such as psilocybin and LSD acutely alter states of consciousness after administration, with a duration of this altered state of consciousness between 4-6 hours (psilocybin) or 12-17 hours (LSD).”

“Given that psychedelics have a unique mode of action and given that they may have antidepressant and anxiolytic properties, it is important to better understand their therapeutic effects,” Kraehenmann told PsyPost. “One crucial element of their therapeutic potential may be the alteration in state of consciousness and subjective experience. However, the subjective experience during psychedelic action is highly variable and difficult to understand. An intriguing similarity between night dreaming and psychedelic imagery led to my interest to investigate psychedelic imagery and its therapeutic implications.”

Twenty-five healthy subjects participated in the double-blind, placebo-controlled study. The findings were published in the peer-reviewed journal Psychopharmacology.

“We found that the prototypical psychedelic drug LSD (lysergic acid diethylamide) produced dreamlike waking imagery,” Kraehenmann explained. “Dreaming was quantified using a specific dream marker: cognitive bizarreness (strange, fanciful quality of thinking) in guided mental imagery reports. In addition, we showed that dreamlike imagery during LSD was related to the effects of LSD on self-boundaries and cognitive control.”

“In sum, we found that dream imagery and psychedelic imagery are closely related: imagery is not only more vivid, diverse and fluent, but also less rational and cognitively constrained. This creative aspect may be a crucial aspect of the therapeutic potential of psychedelic imagery because this may facilitate inner visionary experiences which may be of great value to overcome psychological barriers and anxieties, and to stimulate personal growth.”

Scientists have long known that LSD is a serotonin agonist, meaning it activates certain serotonin receptors. Previous research had found that LSD alters the processing of personal meaning by increasing the activity of serotonin 2A receptors in certain areas of the brain.

But how did Kraehenmann and his colleagues confirm that serotonin receptors were involved in the dreamlike states? They found that the drug ketanserin fully blocked the dreamlike states of consciousness induced by LSD. Ketanserin is a serotonin 2A receptor antagonist, meaning it inhibits activity at serotonin 2A receptors.

Ball-and-stick models of the LSD molecule (left) and serotonin molecule (right).

“The current interest in psychedelic research and therapy is huge and promising,” Kraehenmann told PsyPost. “However, psychedelics are potent modulators of consciousness states, and previous history (e.g. Timothy Leary) has shown that psychedelics should be considered a therapeutic tool in the hands of professional therapists, and not for self-enhancing, pseudo-religious purposes.”

“One way to prevent repetition of history and to minimize adverse long-term effects would be to provide psychedelic therapy within supervised professional settings and to establish guidelines and programs for psychedelic therapist training,” he continued. “We are currently working on such a program. Current psychedelic therapy settings mainly include music listening and interpersonal support. Our studies indicate that guided imagery would be an ideal therapy element for psychedelic therapy.”

“There is a broad overlap between dreaming and psychedelic states,” Kraehenmann concluded. “Grinspoon and Bakalar, in their famous book Psychedelic drugs reconsidered, nicely summarize this in the following way: ‘There are good reasons for applying the term ‘oneirogenic,’ producing dreams, to psychedelic drugs. In its imagery, emotional tone, and vagaries of thought and self-awareness, the drug trip, especially with eyes closed, resembles no other state so much as a dream’.”

The study, “Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation“, was also co-authored by Dan Pokorny, Leonie Vollenweider, Katrin H. Preller, Thomas Pokorny, Erich Seifritz, and Franz X. Vollenweider.