In the practice of medicine at a public university, I often encounter the complaint from my patients that “someone must have slipped something into my drink”. Their rationale is that they have drunk this much on previous occasions, but this time they do not remember anything. I recently was told a story by a fellow medical professional that highlights this issue. On a hot spring Friday evening, upon returning to her dorm room following her collegiate track practice, her friends told her to hurry and shower so they could get to an off-campus party. It had been a week of limited sleep, and she had just completed an exceedingly hard practice in the heat without adequate time to rehydrate. Further, she did not grab dinner before leaving and she had just begun to use an antihistamine to combat spring allergies. Prior to leaving, she took an extra dose of diphenhydramine so her nose would not be dripping at the party. She arrived at the party dehydrated and spotted a cooler containing iced watermelon flavored Seagram’s Escapes bottles. She gulped down two bottles rapidly (3.2 %, 11.2 ounces). She did not recall anything else from that evening. I have puzzled over whether her story was true (“only two drinks” she swore). She stated it was the only time in her life she said that she ever developed a “blackout” and she rarely drank alcoholic beverages before or after that event.
Alcohol accounts for 4% of the global health burden. For those of us who work closely with college students, it is the leading cause of adverse effects in this population. This includes not only the issue of alcohol overdose, but also its association with sexual assault, trauma, poor school performance and youth addiction. The literature clearly demonstrates that nearly half of college students who consume alcohol report having experienced an alcohol-induced blackout (Barnett 2014 PMID: 24411802; White 2002 PMID: 12638993). Surprisingly, 30% of of surveyed students report experiencing an alcohol-induced blackout before the age of 15 (Schuckit 2015 PMID: 25516068).
Now, let’s go back to my young colleague. At a weight of ~40 kg and having just gulped downed two 11.2 ounce bottles rapidly that contained 3.2% ethanol, her blood ethanol level had the potential to rapidly reach ~ 80 mg/dL. I have been dubious that it was in fact two bottles, but she swears it was only two (yes, we all have heard that claim before). She assured me those bottles were sealed and she took the cap off herself and the bottles were in her procession the entire 30 minutes it took to down them .
Based on the medical literature, alcohol-induced blackouts may be complete (“en bloc”) or partial (fragmentary). En bloc blackouts (EB) begin and end at definitive points with full permanent amnesia of the period in between. EB has been described by other authors as not a process of forgetting, but of not remembering (Wetherill 2016 PMID: 27060868). Fragmentary blackouts (FB), also called “gray outs” or “brown outs”, involve a more transient memory loss for which aspects of the experience are recalled in part via pertinent cues.
Alcohol-induced blackouts are often confused with “passing out” from alcohol by the lay public; however, “blacking out” and “passing out” are different states of consciousness. A person experiencing a blackout is conscious and interacting with their environment. A person who has passed out from alcohol has fully lost consciousness and the capacity to engage in voluntary behavior. Memory deficits during a blackout are anterograde, meaning memory loss for events that occurred after alcohol consumption (White 2003 PMID: 15303630). As pointed out in Wetherill’s nicely written review on this topic, short-term memory remains intact during an alcohol-induced blackout (Wetherill 2016 PMID: 27060868) This means an intoxicated person is able to engage in a variety of behaviors, including having detailed conversations and other more complex behaviors like driving a vehicle (albeit not necessarily well), but the information about these behaviors is not transferred from short-term to long-term memory. This results in memory deficits and memory loss for these events . There is no objective evidence that a person is in an alcohol-induced blackout and it can be difficult or impossible to know whether a drinker is experiencing a blackout (Pressman 2013 PMID: 23692320; Goodwin 1995 PMID: 7735016).
Initial research in the 1950s reported that such blackouts were a hallmark of progressive alcoholism. Subsequent research has proved differently, and blackouts are no longer considered as a sign of alcoholism. The majority of people experiencing an alcohol-induced blackout are not clinically alcohol dependent. If you doubt this fact, review the study by Knight who reported that 35% of trainees in a large pediatric residency program had reported experiencing at least one blackout (Knight 1999 PMID: 10555722). I know my pediatric residents well, and certainly 35% are not habitual alcoholics (many are in fact teetotalers).
Risk Factors
So, was my colleague at risk for a blackout and, if so, what were those risks? Older studies have led to the belief that a value of 250 mg/dL is a threshold BAC necessary for producing an alcohol-induced blackout (Goodwin 1970 PMID: 4913709) This, however, has been found to be soundly untrue, and an incorrect extrapolation of preliminary evidence (as often happens, especially with the U.S. news media, as in their improper and markedly overblown association of vaccinations with autism and black mold with pulmonary hemosiderosis. . . .) Additional research has clearly demonstrated that alcohol-induced blackouts occur at BACs far below ta BAC of 250 mg/dL. For EBs, corresponding BACs were found to be as low as 70 mg/dL and for FBs, corresponding BACs were as low as 60 mg/dL (Hartzler 2003 PMID: 12921196).
Studies have also demonstrated that the rate of consumption of alcohol is a key predictor for the development of blackouts. It is not only how much you drink that causes a blackout, but also how fast you drink (Goodwin 1969 PMID: 5804804, Ryback 1970 PMID: 5458472). Not eating also contributes (Goodwin 1969 PMID: 5804804) as it increases the absorption of alcohol. Numerous studies since that time have clearly demonstrated that a rapid rate of increase in BAC is most consistently associated with the occurrence of an alcohol-induced blackout. Therefore, consuming alcohol rapidly on an empty stomach, or drinking higher content alcoholic beverages (e.g. liquor as opposed to a standard beer) are definite risk factors for a blackout.
Studies have also demonstrated that alcohol-induced blackouts are not the result of some previously undiagnosed memory problem in the drinker. Rather, studies have demonstrated that there was no difference in baseline memory between subjects that did or did not experience a blackout. There is, however, clear evidence of individual genetic variability that make certain individuals more vulnerable to alcohol-induced memory impairment. There is also the concern that specific medications being taken may add to the risk of a blackout. There are limited studies, however, that examine the association of specific medications on lowering BAC thresholds for alcohol-induced blackouts. Rather, there are simply warnings on medication package inserts that advise against using the medication with alcohol.
Pathophysiology
So what was occurring within my colleague’s brain when she gulped downed the reported two Seagram’s drinks? Lee published a nice review article that succinctly explains the process (Lee 2009 PMID: 20049223). A blackout is the result of alcohol-induced disruption of memory formation. The formation of memory involves encoding (the initial registration and interpretation of stimuli), storage (consolidation and maintenance of encoded stimuli) and retrieval (which is the search and recovery of stored stimuli). Research has demonstrated that alcohol has its greatest effects on encoding (Wetherill 2016 PMID: 27060868). Short-term memory, which functions over a period of seconds, is relatively spared even during an en-bloc blackout. Long-term memory, which applies on the scale of days to years, established before intoxication, is also maintained. Amnesia for events during intoxication involves impairment of episodic memory. Episodic memory, by definition, includes the time, place, and other interrelated circumstances in which the event occurred. This contextual information is a prerequisite for formation of memories (Hasselmo 2009 PMID: 19615456; Smith 2006 PMID: 16897724). Alcohol’s effect on encoding may disrupt the processing of context for the formation of an episodic memory. Because the episode was encoded with faulty context, free recall of this memory may be particularly difficult or, depending on the degree of encoding impairment, even impossible, as in the case of EB blackouts (Lee 2009 PMID: 20049223).
The cellular mechanism by which a context is generated has been partially elucidated by observation of “place cells” in rodents. Place cells are cells in the rodent brain which fire when the animal is in a particular location in the environment (Silvers 2003 PMID: 14629930). These location-specific cells ultimately create a spatial map in the brain, serving as a framework for event memories created in that environment. These cells, found in the CA1 pyramidal cell layer of the hippocampus, are suppressed by alcohol. This dose-dependent suppression of CA1 pyramidal cells is consistent with dose-dependent effects of alcohol on episodic memory formation. Evidence suggests that cognitive abilities mediated by the hippocampus are particularly sensitive to the effects of alcohol at varying levels (White 2000 PMID: 10973604).
The exact molecular mechanisms of the effects of alcohol on the hippocampus are not clear but likely involves inhibition of NMDA receptors. In neuroscience research the cellular changes leading to memory formation is called long-term potentiation (LTP), which is the establishment of long lasting heightened responsiveness to signals from other cells (Schummers 2001 PMID: 11597760). Ethanol’s effect on LTP in the hippocampus is thought to involve both inhibition of the NMDA receptor and potentiation of the γ-aminobutyric acid A (GABA-A) receptor transmission, which leads indirectly to further NMDA receptor inhibition (Lee 2009 PMID: 20049223).
So, to return to my colleague with her intriguing claim. Based on the evidence found in the literature, my colleague’s story is potentially true. She had a perfect storm of risk factors for sustaining an EB blackout. She was dehydrated, had no food in her stomach, rapidly consumed the alcoholic beverage. In addition, she was a novice ethanol drinker and was taking an over the counter medication (diphenhydramine) in high dose.
However, one other issue must be addressed. Recall bias is problematic in all studies on alcohol, including the ones noted in this report. I recently had an aerospace engineering student with governmental clearance who swore he only drank a “couple” of drinks, had fallen and injured his face, and on emergency department evaluation for his laceration repair, perseverated that he must have been slipped something in his drink. After much discussion, I finally relented to test him – only after he agreed to first check his ethanol level. The level was 143 mg/dL was drawn 8 hours after his injury and his last drink. If you back extrapolate what his potential level was at the time of injury, it would have been well above 250 mg/dL. After talking with his friends who were present, they relayed that he did have a “couple” of drinks prior to going to the bar. At the bar, they all had mixed drinks. A few of them left the table briefly to talk with another group, and upon return discovered the patient had rapidly downed their drinks as well as his own (obviously the other students held a grudge for that action). My patient had no recollection of this. He adamantly believed he only had a “couple” of drinks, when in fact he had at least seven, in rapid succession, per his friends. Blackouts also mean you forget the additional drinks you had. Overall, alcohol-induced blackouts are real entities. In fact, our patients may not be lying to us, because they truly recall only drinking a “couple”. We need better education, especially of youth, about the risks associated with such drinking behaviors and of blackouts. This is something we should not forget.
Diphenydramine is a potent anti-cholinergic. Patient took a high dose and her body weight was small. . Toxiidrome for anti-cholinergics can include delerium and hallucinations
Patient low body weight took large dose of diphenydramine, a potent anti-cholinergic whose toxidrome can include delirium and hallucinations.
You like pretending to be smart, huh.