Ever since Albert Hoffman famously stumbled upon the hallucinogenic properties of lysergic acid diethylamide (LSD) in 1943, scientists have debated whether the drug’s psychoactive effects are harmful or therapeutic. According to a new paper in the journal Psychological Medicine, the substance does indeed have the potential to generate long-term mental improvements, although its immediate acute effects may mirror certain aspects of psychosis.
As such, the researchers have labeled LSD a “paradoxical” compound, since it “can be both a model of, and yet a treatment for, psychopathology.” Based on the evidence presented in the paper, they conclude that the acute effects of psychedelic substances are not necessarily an indicator of their longer-term impacts, and state that “it is arguably the latter that are more clinically relevant.”
During the early years of psychedelic research in the mid-20th century, these substances were thought to be psychotomimetic, meaning they induce a state of psychosis, and therefore provide a useful tool for studying this phenomenon. However, this model later fell out of favor as researchers began using psychoactive drugs to try and bring about positive mood changes rather than psychosis. This approach has been bolstered by several studies in which drugs such as psilocybin, MDMA and LSD have been used to alleviate suicidality, treat addiction and induce enduring feelings of “openness” and positivity.
To attain a greater understanding of how LSD affects users, a team of researchers administered 20 healthy volunteers with a dose of the drug, and asked them to complete a survey called the Psychotomimetic States Inventory (PSI) immediately afterwards. Results showed that participants experienced a number of phenomena associated with psychosis – such as paranoia, anxiety, and delusional thinking – while under the effects of the drug.
However, volunteers also reported experiencing a “blissful state,” which was typically much more pronounced than their sense of anxiety. Speaking to IFLScience, lead researcher Dr. Robin Carhart-Harris said that while there are “stark differences between the acute psychedelic state and psychosis,” there is strong evidence that LSD induces “particular aspects of the very wide range of the phenomenology of psychosis.”
In particular, he believes that the drug’s acute effects place users in a “fragment transitional phase,” in which people feel their sense of self dissolve, often leading to profound feelings of uncertainty and thought disorder. This, he says, strongly resembles the early stages of psychosis.
The acute psychedelic state could provide a useful model for learning how to treat the early stages of psychosis. lassedesignen/Shutterstock
As such, Carhart-Harris claims that the acute psychedelic state may provide a useful model for learning about early psychosis. For instance, by inducing this “heightened plasticity,” whereby individuals become highly vulnerable and malleable, drugs like LSD could enable therapists to improve their understanding of how best to “help [patients] make sense of this strange, uncertain state.”
Taking their study a step further, the researchers asked participants to complete a second set of scientifically certified questionnaires two weeks after ingesting the LSD. At this stage, not only was there no evidence of lingering psychotic symptoms, but volunteers also reported heightened feelings of positivity, indicating that the mid-term effects of the drug may indeed have therapeutic potential.
Though the neurological mechanisms by which LSD is able to induce contradictory psychotomimetic and therapeutic effects are poorly understood, the researchers suggest that this may be related to the drug’s ability to bind to a serotonin receptor called 5-HT2AR. Previous studies have suggested that this receptor may play a role in creative thinking, positive mood, and anxiety, indicating that it could mediate many of LSD’s acute and longer-term effects.
This work was conducted as part of the Beckley/Imperial Research Programme