Brazilian researchers reviewed a series of published studies to draw further insight into the effects of combined ketamine and alcohol use. Findings were analyzed in conjunction with known molecular interactions of ketamine and alcohol throughout the body to conclude that when used in combination, the substances held the potential to negatively impact a number of organs including the liver, gallbladder, heart, and kidneys, while also increasing the risk for adverse behavioral and mental disorders including psychosis.
The research also suggested:
- When used together, ketamine and alcohol have the potential to intensify the effects of either substance when used alone including intensified withdrawal effects and an increased risk of death
- There is a current deficit of medical literature focused on the impact of ketamine and alcohol abuse on various bodily organs with the exception of the brain
- Though there have been many published studies on the medical use of ketamine, studies covering recreational use of the drug are limited
- Greater efforts must be dedicated to drawing out the nature of toxic mechanisms, effects, and clinical outcomes related to the co-abuse of ketamine and alcohol to provide greater knowledge and awareness to the growing community of recreational ketamine users as well as for medical practitioners who may be better equipped to employ new therapeutic strategies as a result
While alcohol is still the most consumed psychoactive substance throughout the globe, there has been a rise in psychoactive substance abuse including ketamine worldwide. A relationship has been observed in fatal and non-fatal overdoses following the use of a litany of recreational drugs in combination with alcohol, suggesting several possibilities including the role alcohol may play in intensifying the physiological or psychological damage normally caused by substances of abuse. The potential role of alcohol is further highlighted in statistics pertaining to ketamine-related emergency department visits, as such visits often involve the use of other substances in tandem with ketamine, however up to 71.5% of visits are those where alcohol is identified as the co-ingested substance. When ketamine use precedes death, post-mortem chemical examinations for intoxicants rarely find ketamine alone. Other substances frequently misused with ketamine include amphetamines, MDMA, cocaine, and caffeine. Though studies have indicated the relationship between recreational ketamine and alcohol co-ingestion, with trends to statistically support the potentially dangerous outcomes that may transpire, e.g., overdose or death, very few studies have examined the effects that the simultaneous use of these substances may specifically have on a litany of bodily organs and systems.
For example, signs of liver damage ranging from minor metabolite alterations to liver failure have been seen in both ketamine abusers and alcohol abusers. Similarly, the toxic effects of both ketamine and alcohol are dose-dependent (becoming more toxic with increasing dose), with toxic events related to each substance noted to persist even during withdrawal. The effect of alcohol on the liver has been widely documented, however although ketamine is known to potentially cause liver damage, the exact mechanism for this is still unclear.
Authors drew upon ketamine’s known interactions with the liver enzyme cytochrome P-450 (CYP P-450), which act to ramp up the enzyme’s metabolic mechanism of action causing a breakdown of fatty acid metabolites that are also seen in livers damaged by alcohol. Chronic alcohol also induces the CYP-450 enzyme into overdrive causing a buildup of fat in the liver and cellular damage. After significant cell death over time the liver scars and damage cannot be reversed, a sign of liver failure known as cirrhosis.
Because of the similar effects that alcohol and ketamine play on the liver, its enzymes, and breakdown products, authors suggested that the co-abuse of ketamine and alcohol may elicit cirrhosis, however could only find one report in published medical literature highlighting symptoms resulting from damage to the liver and its drainage system due to ketamine and alcohol use. The only study authors could find that explored their hypothesis in greater depth was one involving mice and monkeys rather than human patient subjects, suggesting that the molecular pathways by which alcohol and ketamine may interact together were of little importance or relevance to clinicians and medical researchers. Such pathways are important to elicit and understand as they may provide a basis for formulating precision treatment and prevention measures.
The relatively lax schedule III controlled substance designation assigned to ketamine in comparison to more stringently regulated, widely known and deadly drugs of abuse such as opioids (schedule I) has in part cloaked trends of increasing usage and adverse outcomes including addiction from the attention of regulatory bodies and medical practitioners. As ketamine continues to be used both medically and recreationally, it is essential to first increase awareness of its potential dangers so that effective management schemes may be cultivated for patients who are prescribed and administered ketamine to recreational users alike. Such an approach may involve a diverse team of doctors, pharmacists, nurses, and mid-level practitioners.
