Tag: alcohol use disorder

Categories : AddictionTags :

Ketamine High not Why Treatment Works for Acohol Use Disorder, Study Finds

On By ModernMedia
Photo by Bruce Christianson on Unsplash

The psychedelic effects recreational users often seek from taking ketamine do not predict the therapeutic benefits for people being treated for alcohol use disorder, according to new research from King’s College London and University of Exeter.

The popular theory, which says that ketamine may have its therapeutic benefits because it produces strong psychedelic effects, has been called into question by the new study, published in Addiction. The findings suggest the treatment response may be down to other effects of the drug. 

The research, led by the Institute of Psychiatry, Psychology & Neuroscience at King’s, is the largest randomised controlled trial to date examining the use of intravenous ketamine-assisted psychotherapy for individuals with moderate to severe alcohol use disorder. It uses data from the Ketamine for reduction of Alcoholic Relapse (KARE) clinical trial at the University of Exeter and University College London.

For the first time, we thoroughly investigated the acute psychoactive effects of repeated ketamine infusions in people with alcohol use disorder. The effects didn’t predict ketamine’s therapeutic benefit, which leaves open other psychological or neural mechanisms that need to be investigated.

Dr Will Lawn, Senior Lecturer at King’s College London and study lead

Researchers carried out a secondary analysis of the KARE clinical trial which was conducted at two clinical research facilities in England involving 96 adult participants and sought to clarify the role of ketamine’s psychoactive effects in supporting abstinence from alcohol. 

Participants receiving three weekly infusions of intravenous ketamine reported marked psychoactive experiences, including altered reality, out-of-body sensations, and perceptual distortions, compared to those receiving placebo. These effects were consistently strong across all three dosing sessions. This suggests little to no development of tolerance to ketamine’s subjective effects over the short dosing schedule.

But despite the pronounced psychoactive effects, the study found no significant evidence that these experiences mediated ketamine’s therapeutic benefit in reducing alcohol consumption. The percentage of days abstinent from alcohol over six months was not predicted by the intensity of subjective drug effects.

A larger trial will explore ketamine’s effects in brain connection and function changes, as well as dosing.

Source: King’s College London

Categories : Substance UseTags :

Repurposed Anti-inflammatory Drug may Help Treat Pain from Alcohol Use Disorder

On By ModernMedia
Photo from Pixabay CC0

A Scripps Research study has found that a drug already FDA-approved for treating inflammatory conditions may help reduce both alcohol intake and pain sensitivity in alcohol use disorder (AUD).

The results, published in JCI Insight, suggest that the drug apremilast, a phosphodiesterase-4 (PDE4) inhibitor, or a compound that blocks an enzyme involved in inflammation, could be repurposed as a dual-acting therapy for AUD, particularly in individuals who have pain during and after alcohol use.

AUD affects an estimated 400 million people aged 15 years or older, according to the World Health Organization. Chronic pain is one of the strongest predictors of alcohol relapse, yet it’s often overlooked in AUD treatment strategies. People with AUD frequently experience mechanical allodynia as well, a condition in which even light touch is perceived as painful. This sensitivity can persist during abstinence and contribute to ongoing alcohol use and relapse.

“Our findings highlight the therapeutic value of apremilast to reduce co-occurring drinking and mechanical allodynia in long-term abstinence – a critical component of harmful drinking and AUD psychopathology,” says senior author Marisa Roberto, a professor of neuroscience at Scripps Research.

Currently FDA-approved for treating psoriasis (a chronic autoimmune skin condition) and psoriatic arthritis (a related joint disease), apremilast has previously been shown to reduce alcohol drinking in both mice and humans. The new study builds on that work by examining whether apremilast could also ease pain linked to alcohol exposure.

To investigate, the research team tested apremilast in a type of rat genetically predisposed to higher alcohol consumption and in a standard genetic strain of rats. Both rat strains were given access to alcohol and treated with either apremilast or a placebo.

Apremilast significantly reduced alcohol intake across strains and biological sexes. It also decreased pain sensitivity in most groups, both immediately after drinking and during abstinence, ranging from 24 hours to four weeks after alcohol had been removed.

“But at specific time points, the patterns of reduction differed between males and females, as well as between strains,” notes first author Bryan Cruz, a postdoctoral fellow at Scripps Research. For example, the pain-relieving effects of apremilast weren’t observed in some of the male rats, underscoring the importance of considering biological sex in future studies.

In another set of experiments, apremilast increased GABAergic transmission. a type of inhibitory signaling that helps regulate pain and stress signalling, in the central amygdala, which is involved in both addiction and pain. This effect was only observed in the standard strain of rats, suggesting that apremilast’s impact on brain signalling may depend on genetic background or vulnerability to AUD.

In both strains of male rats, alcohol exposure increased expression of PDE4 genes in the brain, further supporting a link between inflammation, pain and compulsive alcohol use. While other PDE4 inhibitors have been studied for pain unrelated to alcohol consumption, apremilast may offer a path toward more personalized therapies for those with both AUD and pain. But clinical research is still needed to determine the drug’s efficacy for such conditions in humans.

Going forward, the researchers also plan to explore whether apremilast can mitigate anxiety and other negative emotional states that commonly emerge during alcohol withdrawal.

“For over a decade, it’s been well-established that withdrawal-induced anxiety is a major driver of relapse,” points out Roberto. “Therefore, addressing other key components of the addiction cycle is critical, as many individuals use alcohol to cope not only with physical pain but with emotional distress as well.”

Source: Scripps Research Institute