LSD decreases binge-like drinking in a rodent model of alcoholism, but only temporarily

New research has found that lysergic acid diethylamide (LSD) briefly reduces binge-like alcohol consumption in mice but does not produce long-lasting effects. The findings, which appear in the Journal of Psychopharmacology, suggest that the psychedelic substance by itself does not produce lasting changes in alcohol drinking behavior.

In recent years, there has been a renewed interest in psychedelics as potential therapies, particularly for addictions. A growing body of research suggests that psychedelics, when combined with psychotherapy, may help to break the cycle of addiction. Despite these promising results, very few studies have examined the influence of LSD on reward-linked behaviors in rodents.

“We were intrigued to know whether the long-lasting reducing effects on alcohol drinking caused by a single dose of a psychedelic drug as shown in some studies with human patients would also be true in a mouse model,” explained study author Lauri Elsilä, a doctoral researcher at Esa Korpi’s Neuropsychopharmacology Lab at the University of Helsinki. “The broader core question driving the research in general, of course, is ‘how do psychedelic compounds work?'”

Alcoholism is a serious problem that affects millions of people around the world. Although there are many effective treatments available, there is still a need for better understanding of the disease. One way to study alcoholism is through the use of rodent models. By observing how rodents behave when given access to alcohol, researchers can gain insights into the neurological and behavioral changes that occur with chronic alcohol use. Additionally, rodent models are frequently used to test potential treatments for alcoholism.

“One of the main advantages in using rodent models in psychedelic research is the possibility of studying molecular mechanisms with tools not available in humans,” Elsilä and his colleagues noted.

For their new study, the researchers tested the impact of LSD on male mice who had been habituated to alcohol over the course of four weeks. The alcohol was only available for a two-hour period on four consecutive days per week. During the fifth week, the mice were treated with either an inert saline solution or LSD, and then immediately given access to alcohol.

Elsilä and his colleagues found that mice who had received 0.1 mg/kg LSD treatment displayed reduced alcohol intake during the two-hour period compared to mice who received the saline solution, indicating that LSD had acute effects on alcohol consumption. But the researchers observed no further effects on the following days when alcohol was made available.

“In this set of experiments, LSD would only reduce binge-like ethanol drinking acutely without any observable long-lasting effects,” Elsilä told PsyPost. “This, together with other rodent work, points one towards thinking that psychedelic drugs on their own don’t have any inherent, persistent healing effects, but need something further for the therapeutic effects, which in human trials of course most likely is the added therapeutic work alongside the psychedelics.”

The researchers conducted a similar experiment using sucrose (table sugar) instead of alcohol, but found no evidence that LSD affected sucrose intake. LSD also did not appear to significantly influence the rewarding effects of amphetamine. “The reductions in the acute intake were much more prominent with alcohol than with other rewarding things, raising interesting questions on the reasons behind that,” Elsilä said.

While rodent models have helped to advance our understanding of alcoholism, they are not perfect substitutes for human subjects. Ultimately, more research is needed to fully understand the effects of psychedelic substances on alcoholism in humans.

“As with any rodent work, one should be very careful when trying to extend the findings to humans, even if some of the reward-related processes might be quite similar in many mammalian species,” Elsilä explained. “In general, I think that this study raised even more questions than it ended up answering, as research maybe always should. In my mind the most interesting questions to be addressed are 1) why is the reducing effect on ethanol so much bigger than on sugar, and 2) what would it need to show similar long-lasting reductions in alcohol drinking in mice as there have been in human studies?”

“There’s a lot of hype around psychedelics and research around them,” Elsilä added. “I would advise anyone interested in the topic to take everything said about the drugs – especially about their medical promises – with a pinch of salt: at least when it comes to the medical evidence of psychedelics’ therapeutic potential, the evidence is still lacking, even if highly promising and intriguing.”

The study, “Effects of acute lysergic acid diethylamide on intermittent ethanol and sucrose drinking and intracranial self-stimulation in C57BL/6 mice“, was authored by Lauri V. Elsilä, Juliana Harkki, Emma Enberg, Alvar Martti, Anni-Maija Linden, and Esa R. Korpi.

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