The effects of simultaneous alcohol and cannabis use on subjective drug effects: A narrative review across methodologies

Abstract

Over 75% of young adults who use cannabis also report drinking alcohol, leading to increased risks including impaired cognition, substance use disorders, and more heavy and frequent substance use. Studies suggest subjective responses to either alcohol or cannabis can serve as a valuable indicator for identifying those at risk of prolonged substance use and use disorder. While laboratory studies suggest additive effects when using alcohol and cannabis together, the impact of co-using these substances, specifically with respect to cannabidiol, on an individual's subjective experience remains unclear. This narrative review explores the effects of simultaneous alcohol and cannabis (SAM) use on subjective drug effects, drawing from qualitative research, laboratory experiments, and naturalistic studies. Experimental findings show inconsistency in the combined effects of alcohol and cannabis, likely influenced by factors such as dosage, method of administration, and individual substance use histories. Similarly, qualitative and naturalistic studies show mixed results regarding subjective drug effects following simultaneous alcohol and cannabis use. These discrepancies may be due to recall biases, variations in assessment methods and how patterns of SAM use and related experiences are measured in real-world contexts. Overall, this narrative review highlights the need for more comprehensive research to better understand subjective drug effects related to the SAM use in diverse populations and settings, emphasizing the importance of frequent and nuanced assessment of SAM use and subjective responses in naturalistic settings.

Introduction

Alcohol and cannabis are the most widely used substances among young adults (aged 18-30) in the U.S, with 66.3% reporting alcohol use and 28.5% reporting cannabis use in the past month (Patrick et al., 2022). This demographic also has the highest incidence of alcohol use disorder (AUD) and cannabis use disorder (CUD) (Hasin, 2018). Substantial exposure to these substances increases the likelihood of deleterious psychosocial and behavioral outcomes (Volkow et al., 2014; White and Hingson, 2013). While much of the research focuses on outcomes related to the exclusive use of either substance, over 75% of individuals who use cannabis also report drinking alcohol (Barrett et al., 2006; Midanik et al., 2007; Patrick et al., 2018). Co-using these substances place individuals at an increased risk for more severe and problematic outcomes such as altered brain function, decreased academic performance, poorer mental health and cognition, driving under the influence, and greater likelihood of developing a substance use disorder relative to the use of alcohol or cannabis alone (Claus et al., 2018; Karoly et al., 2020; Patrick et al., 2021; Pritschmann et al., 2022; Thompson et al., 2021).

Co-use is a comprehensive term commonly used to encompass a wide range of substance use behaviors, spanning co-administration, concurrent, and simultaneous use. Concurrent use is typically characterized as using both substances "at least once in the past month/year" or "on the same day," without specifying whether both substances were consumed together or within a specific timeframe (Arterberry et al., 2020; Gunn et al., 2022a; Metrik et al., 2019). Conversely, definitions of simultaneous (SAM) use vary widely in the literature. Earlier studies characterize simultaneous use as using both substances “at the same time”, “on the same occasion/event”, and “in combination” (Brière et al., 2011; Collins et al., 1998; Earleywine and Newcomb, 1997; Martin et al., 1996). More recent research defines simultaneous use as the use of both substances “so that the effects overlap” and “at the same time, so their effects overlapped” (Lee et al., 2017; Lipperman-Kreda et al., 2017; Patrick et al., 2018; Terry-McElrath et al., 2013). Co-use can also refer to co-administration, commonly observed in laboratory settings, such as the use of one substance immediately before/after the other (D’Amico et al., 2020). A recent review examining the effects of alcohol and cannabis co-use on neurocognitive function highlights the lack of consensus among many studies regarding methodology and definitions of co-use (Bedillion et al., 2021). Given the considerable variation in the definitions of co-use across studies, this may limit both our understanding of SAM use effects and the reproducibility of findings among different subgroups of individuals. For the purpose of this review, and due to the lack of consistency in the existing literature, co-administration will be used when referring to SAM use in laboratory studies and SAM use will be used to refer broadly to the use of substances so the effects overlap.

Of the many factors examined as an early indicator of sustained and problematic substance use, subjective responses to alcohol and cannabis use serve as a valuable indicator for identifying individuals at risk for continued use and substance use disorders (Fergusson et al., 2003; King et al., 2021; Le Strat et al., 2009; Scherrer et al., 2009; Zeiger et al., 2010). Subjective responses, often referred to as subjective effects, are typically defined as the combination of pharmacological and expectancy effects on mood and behavior. These effects are often characterized into valence (e.g., positive, negative) and arousal (e.g., stimulating, sedating) domains (Morean and Corbin, 2010). While laboratory studies provide strong evidence for the additive or synergistic effects of combining alcohol and cannabis, there are mixed findings related to the effects of SAM use on subjective responses when examined qualitatively and in real-world settings. Notably, the majority of research focuses on the main psychoactive constituent of cannabis, tetrahydrocannabidiol (THC), when examining the effects of co-using with alcohol on subjective responses. However, cannabidiol (CBD), the second most prevalent cannabis constituent has gained considerable attention for its potential therapeutic value. Research on the interaction between CBD and alcohol is limited, predominantly in the context of subjective drug effects.

Prior reviews and discussions within the literature offer valuable insight into the effects of SAM use in clinical laboratory settings (Yurasek et al., 2017) and examine the impact of cannabis use on alcohol use and consequences (Gunn et al., 2022b). While these reviews separately examine subjective drug effects of SAM use across laboratory and naturalistic studies, they do not consider qualitative research nor studies focused on the effects of CBD and alcohol. The purpose of this narrative review is to extend prior work by examining the effects of simultaneous alcohol and cannabis use on subjective drug effects across multiple research methodologies including qualitative research, laboratory experiments (THC and CBD), and naturalistic studies.

Methods

PubMed and Scopus databases were searched for articles examining the effects of alcohol and cannabis co-use on subjective drug effects using the following search terms: cannabis, marijuana, THC, tetrahydrocannabinol, CBD, cannabidiol, ethanol, EtOH, alcohol, co-use, polysubstance use, concurrent alcohol and cannabis use, simultaneous alcohol and cannabis use, co-administration of alcohol and cannabis, intoxication, subjective intoxication, abuse liability, subjective drug abuse liability effects, and subjective drug effects. Reference lists of the articles reviewed were searched to identify any relevant articles not returned by the literature search. To help provide clarity on the complex and nuanced effects of SAM use, findings in each section and in Table 1, are presented in order of qualitative, laboratory, and naturalistic examination.

Table 1.

Summary of studies published reporting on simultaneous alcohol and cannabis use and subjective drug effects.

Author and Year	Sample Size (N)	Outcome	Comparative Results of SAM Use:
			Alcohol	Cannabis
Qualitative Examination
Boyle et al., 2021	38	Open-ended question	Variability in how participants evaluated SAM use events (e.g., no preference, preferred SAM use, and preferred single-substance use)
Waddell et al., 2023	443	Open-ended question	SAM use maps onto domains of alcohol-only effects, distinct domains (e.g., balancing/replacement effects, altered sensations/perceptions)	NA
Experimental Examination
Cannabidiol
Belgrave et al., 1979	15	VAS	↔ Intoxication	NA
Consroe et al., 1979	10	DRS	↔ DRS	NA
Bird et al., 1980	161	VAS	↔ Intoxication	NA
Karoly et al., 2023	36	BAES, SAES	↔ BAES, SAES	NA
Tetrahydrocannabinol
Chesher et al., 1976	12	POMS	↔ POMS	NA
Perez-Reyes et al., 1988	6	VAS	↔ Intoxication	↔ Intoxication
Chait and Perry, 1994	14	ARCI, POMS, VAS	↔ ARCI, POMS, VAS	↔ ARCI, POMS, VAS
Lukas et al., 2001	22	VAS	+ Euphoric (compared to low dose alcohol/THC)
Ronen et al., 2010	12	DEQ, VAS	+ DEQ (want more), Sedation	+ DEQ (want more), Sedation
Raemakers et al., 2011	21	VAS	↔ Drunkenness	↔ High
Ballard deWit et al., 2011	11	ARCI, BAES, DEQ, POMS, VAS	↔ ARCI, BAES, POMS + DEQ (want more)	↔ ARCI, POMS
Hartman et al., 2016	19	VAS	↔ High, Good, Stimulated, Stoned, Sedated, Restless	+ High, Good, Stimulated, stoned, Sedated ↔ Restless
* Fares et al., 2022	28	VAS	+ Drug effects, Like, Good, Bad, Rush, Dizzy, High, Drunk, Exhilarated, Drowsy Nauseated	+ Drug effects, Like, Good, Bad, Rush, Dizzy, Drunk, Exhilarated, Drowsy Nauseated ↔ High
* Wickens et al., 2022	28	ARCI, POMS	+ ARCI, POMS	↔ ARCI, POMS
Schnakenberg Martin et al., 2023	18	VAS	+ High, Buzzed, Drowsy	+ Buzzed
Naturalistic Examination
Lee et al., 2011	779	SHAS-7 (alcohol, cannabis, SAM)	+ SHAS-7	↔ SHAS-7
Linden-Carmichael et al., 2020	154	VAS	↔ Intoxication (day)	↔ Intoxication (day)
Sokolvosky et al., 2020	341	VAS	+ Intoxication (day)	+ Intoxication (day)
Waddell et al., 2023	85	SEAS	+ High/low arousal positive, low arousal negative (moment/day) + High/low arousal positive (person)	NA

Notes: + Greater; − Lower; ↔ No difference. *Studies with matching superscripts derived participants from the same overall sample. ARCI – Addition Research Center Inventory; BAES – Biphasic Alcohol Effects Scale; DEQ – Drug Effects Questionnaire; NA – Not Applicable; POMS – Profile of Mood States; SAM – Simultaneous Alcohol and Marijuana Use; DRS – Subjective Drug Reaction Scale; SEAS – Subjective Effects Alcohol Scale; SHAS – Subjective High Assessment Scale; VAS – Visual Analog Scale

Differences in Subjective Drug Effects Resulting from Simultaneous Alcohol and Cannabis Use.

“Cross-faded”, or being simultaneously intoxicated by alcohol and cannabis, is a common term in the lexicon of many young adults (Abrams et al., 2022; Patrick and Lee, 2018). Theoretical models of substance use suggest that individuals engage in SAM use to either complement, that is to experience an enhanced or additive effect of using the substances together, replace/substitute one substance for the other, or counter the effects of the other substance. Research shows that complementary patterns of alcohol and cannabis use is associated with heavier drinking (Patrick et al., 2020; Subbaraman, 2016). There are a number of ways to measure subjective effects of both alcohol and cannabis, which include:

1. Profile of Mood States (POMS) which is a 72-item measure designed to evaluate mood dimensions including tension-anxiety, depression-dejection, anger-hostility, friendliness, confusion, fatigue, vigor, elation, arousal, and positive mood (McNair, 1971).

2. Visual Analog Scales (VAS) that use a 0-100-mm line anchored with ‘not at all’ and ‘extremely’ to assess subjective drug effects including ‘drug effects’, ‘liking drug effects’, ‘good effects’, ‘bad effects’, ‘stimulation’, ‘sedation’, ‘high’, ‘drunk’.

3. Drug Effects Questionnaire (DEQ) which assesses the strength and desirability of substance effects including ‘drug effects’, ‘liking drug effects’, ‘high’, ‘want more’ (Morean et al., 2013b).

4. Biphasic Alcohol Effects Scale (BAES) which is a 14-item adjective rating scale to assess stimulation and sedation of alcohol (Martin et al., 1993).

5. Addiction Research Center Inventory (ARCI) which consists of six empirically derived scales to measure drug-induced euphoria (morphine-benzedrine; MBG), stimulant-like effects (amphetamine; A), intellectual efficiency and energy (benzedrine group; BG), sedation (pentobarbital-chlorpromazine alcohol group; PCAG), dysphoria and somatic effects (lysergic acid; LSD), and cannabis effects (M) (Chait et al., 1985; Martin et al., 1971).

6. Subjective High Assessment Scale (SHAS-7), which is a 7-item measure of both positive (e.g., ‘happy’, ‘relaxed’, ‘high’, ‘intoxicated’) and negative (e.g., ‘nauseated’, ‘clumsy’, ‘dizzy’, ‘confused’) experiences of alcohol, but can be modified to measure subjective effects related to cannabis use and SAM use (Eng et al., 2005; Schuckit et al., 1997a, 1997b).

7. Subjective Effects of Alcohol Scale (SEAS) which consists of 14 items corresponding to a four-factor model categorizing effects into affective quadrants: high arousal positive, high arousal negative, low arousal positive, and low arousal negative (Morean et al., 2013a).

8. Subjective Drug Reaction Scale (DRS) which assesses seven factors as follows: perception of state, alertness and attention, physical feelings, perception, emotion, cognitive, and sociability (Karniol et al., 1974).

While incorporating a diverse range of subjective drug effects measures allows for a comprehensive evaluation of the effects of SAM use, it presents challenges in terms of synthesizing and summarizing the literature.

Qualitative Examination of Simultaneous Alcohol and Cannabis Use.

Qualitative research allows for a detailed exploration of individual’s experiences, perceptions, and behaviors related to substance use, providing a deeper understanding of lived experiences that complements quantitative approaches. These measures are particularly valuable in understanding dynamic and evolving phenomena, such as substance use behavior among young adults. However, only two studies using qualitative methods have examined subjective drug effects related to SAM use.

Among heavy drinking college students (4/5 drinks women/men in a single occasions at least weekly) qualitative interviews of SAM use experiences were conducted to better understand evaluations of SAM use events (Boyle et al., 2021). Findings show that subjective evaluations of how positive or negative a SAM use event was (compared to alcohol) differed across people and was inconsistent across events when individuals were asked to compare alcohol use nights to SAM use nights. Subjective evaluations depended on patterns of use (e.g., effects of SAM use similar to alcohol when cannabis was used at the end of the drinking event), negative and positive consequences experienced during SAM use (e.g., drinking less during these events, feeling more in control, feeling dizzy, more intoxicated), and external and internal context (e.g., mood, location, event type) (Boyle et al., 2021). In a separate sample (N=443) of college students who engage in SAM use, students were asked to describe how their alcohol effects differ on SAM use versus alcohol-only use days (Waddell et al., 2023b). The study identified nine concepts related to SAM (vs. alcohol-only) use subjective effects which included: increased/decreased impairment, low arousal/relaxation, balancing/replacement effects, “cross-faded” effects, little-to-no-differences, altered sensation and perception, increased negative affective states, increased appetite, and increased/decreased negative consequences. While many of these domains overlap with constructs commonly used to assess alcohol use effects, SAM use included distinct domains such as altered sensations and perceptions and increased negative affectivity. Notably, neither qualitative study assessed subjective effects of SAM use versus cannabis-only and thus it is unclear whether subjective effects of SAM use are similar to cannabis use alone.

Summary of Qualitative Findings

Findings from these qualitative studies suggest perceptions and subjective evaluations of SAM use embodies considerable heterogeneity across individuals and events, which may be used to inform future quantitative research in this area. However, it should be noted that there were only two qualitative studies, both of which were conducted in college student samples, which may not represent the experiences of the broader population of individuals who engage in SAM use. Researchers should consider reactive/situational factors, variability in terms of drinking and cannabis use levels, and distinct domains with respect to subjective evaluations of SAM use versus single-substance alcohol and cannabis effects. More qualitative research with diverse samples is needed to validate a measure of subjective effects of SAM use.

Experimental Examination of Simultaneous Alcohol and Cannabis Use.

Research involving the separate administration of alcohol and cannabis shows that each substance has individual effects on subjective responses. For example, ad-libitum smoking of cannabis [12.5% THC] significantly increases arousal, positive mood, confusion, friendliness, and elation, along with a decrease in fatigue (Matheson et al., 2020), whereas the administration of oral CBD (15mg, 300mg, 1500mg) show no significant differences in ratings of ‘stoned’, ‘sedated’, ‘alert’, or ‘sleepy’ (McCartney et al., 2022). The administration of high (0.8 g/kg) and low (0.4 g/kg) doses of alcohol significantly increases ‘feel drug’, ‘‘stimulation’, ‘liking’, and ‘want more’, compared to placebo (King et al., 2011). However, less is known about how cannabis, and its constituents, may interact with alcohol and impact subjective responses.

Cannabidiol and Alcohol

CBD is the second most prevalent cannabis constituent, with a favorable abuse liability profile given it does not produce typical behavioral cannabimimetic effects (e.g., psychoactive). Recent qualitative work shows that 51.4% of young adults have used CBD in their lifetime and 32% have used CBD in the past six months (Wysota et al., 2022). CBD is perceived as safe, socially acceptable, and effective for addressing a range of physical and psychological symptomology across this age group. Clinical research on CBD has demonstrated promise in treating physiological conditions (e.g., epilepsy, parkinson’s disease) and substance use disorder (Pauli et al., 2020). Notably, it is not uncommon for young adults who use CBD-dominant products to also report alcohol use (Fedorova et al., 2021). Although prior research highlights the clinical utility of CBD, research on the effects of CBD and alcohol is severely limited. Only four studies have examined the effects of co-administration of CBD and alcohol on subjective effects.

Some of the earliest studies in this area of research found that varying doses of CBD (2.5mg, 5mg, 10mg, 20mg) did not significantly affect intoxication ratings of alcohol (0.54g/kg) (Belgrave et al., 1979; Bird et al., 1980). In line with the previous findings, Consroe and colleagues found that the effects of CBD (200mg) combined with alcohol (1g/kg) on subjective responding of the DRS were identical to alcohol alone (Consroe et al., 1979). Since these earlier studies, only one study has followed up on this line of work. Karoly and colleagues administered CBD (30mg, 200mg) and a standard dose of alcohol (0.6g.kg) to examine the effects on the BAES and SEAS. Findings from this study show a significant difference between 200mg of CBD and alcohol alone on changes in stimulation and sedation (BAES subscales), such that 200mg of CBD was associated with a slower reduction in stimulation during the descending limb of the blood alcohol concentration (BrAC) curve. However, the authors concluded that the overall effects of CBD on subjective effects of alcohol were minimal, given the small magnitude of differences between slopes and the wide Bayesian credible intervals. The limited number of experimental studies in this area, highlights a significant gap in the current research. Given the small sample sizes across studies, with the exception of one, this poses a concern regarding the limited statistical power, and ability to extrapolate the findings to more diverse and representative samples. Furthermore, future research should consider exploring the effects of SAM use on subjective drug effects in daily life, in the context of CBD-dominant products.

Tetrahydrocannabinol and Alcohol

Profile of Mood States

In early studies exploring the combined effects of alcohol and cannabis on POMS measures, no significant effects were observed (Chait and Perry, 1994; Chesher et al., 1976). In a small sample of (N=12) of young adults (aged 18-29), characterized by mild drinking histories and previous cannabis exposure, co-administering alcohol (0.54g/kg) and oral cannabis (10mg THC capsule) did not result in significant increases in tension/anxiety, depression/dejection, anger/hostility, vigor, or fatigue across 160 minutes, compared to either substance alone (Chesher et al., 1976). Consistent with the study conducted by Chesher and Colleagues, a similar study, in a separate sample (N=14), also did not observe significant increases in anxiety, depression, anger, vigor, fatigue, confusion, friendliness, or elation after co-administration of alcohol (0.6g/kg for men, 0.5g/kg for women) and smoked cannabis (3.6% THC) across 180 minutes compared to either substance alone (Chait and Perry, 1994). In an effort to replicate and extend previous research, Ballard and de Wit recruited young adults (N=11) and administered oral cannabis (2.5mg THC dronabinol capsule) with either a low (0.1g/kg) or moderate (0.2g/kg) dose of alcohol (Ballard and de Wit, 2011). The within-person interaction of alcohol and cannabis did not result in statistically significant effects on any measure of the POMS. Given the relatively small sample size (N=11), this study may lack the statistical power necessary to detect significant within-person effects. Despite the absence of significant findings, these studies concluded that the combined effects of alcohol and cannabis tend to be additive, and in some instances, appeared to counteract each other’s effects (Ballard and de Wit, 2011; Chait and Perry, 1994; Chesher et al., 1976). Incongruent conclusions may be due to differences in the order of substance administration, although the effects of order were not a direct aim of this research. Karoly and colleagues (Karoly et al., 2022) recently proposed a mobile laboratory study to examine order effects (cannabis concentrates before alcohol vs. alcohol before cannabis concentrates) on objective and subjective intoxication. To date, only one study has examined order of alcohol and cannabis use on consumption and consequences at the day-level and found that using cannabis first on a co-use day is associated with lower daily alcohol consumption, but greater daily cannabis consumption (Gunn et al., 2021a). However, the effects of order on subjective drug effects was not examined. More recent work by Wickens and colleagues shows that, among a larger sample (N=28) of young adults who used cannabis weekly and reported heavy episodic drinking [consuming at least 5 drinks (men) and 4 drinks (women) within 2 hours], the combined effects of alcohol (target BrAC of 80 mg/dL) and smoked cannabis (12.4% THC) were associated with a significantly greater mean difference score in tension-anxiety and confusion, compared to placebo, with no significant differences in change scores when compared to alcohol or cannabis alone (Wickens et al., 2022). Notably, administration of alcohol alone led to significantly greater mean difference scores in confusion compared to alcohol and cannabis combined.

Although these studies add to our limited knowledge of the effects of co-administration, results across studies are inconsistent. This may be due to the varying sample sizes, differing methodological approaches (e.g., dose of alcohol and cannabis, method of cannabis administration), and difference in sample recruitment (e.g., frequency of cannabis use and alcohol consumption, ranging from light-to-moderate and heavy episodic drinking). Taken together, these studies support the need for additional research to provide a more nuanced understanding of the interaction between alcohol and cannabis on dimensions of mood. Future research should consider including larger and more diverse samples and a broader range of alcohol and cannabis dosages to more clearly delineate the effects of SAM use.

The Addiction Research Center Inventory

When assessing subjective drug effects using the ARCI, studies also show inconsistent findings. Combining alcohol (0.6g/kg for men, 0.5g/kg for women) with smoked cannabis (3.6% THC) (N=14) does not result in significant changes in euphoria (MBG), stimulation (A), intellectual efficiency and energy (BG), sedation (PCAG), dysphoria (LSD), cannabis effects (M) across 180 minutes, compared to alcohol or cannabis alone (Chait and Perry, 1994). Consistent with this work, Ballard and Colleagues show that the within-person interaction of oral cannabis (2.5mg THC dronabinol capsule) with either low (0.1g/kg) or moderate (0.2g/kg) doses of alcohol did not result in a significant change on subscales of the ARCI compared to alcohol or cannabis alone (Ballard and de Wit, 2011). Furthermore, in a study with a larger sample (N=28), the co-administration of alcohol (target BrAC of 80 mg/dL) and smoked cannabis (12.4% THC) resulted in significantly greater euphoria (MBG), compared to alcohol alone and placebo (Wickens et al., 2022). Additionally, co-administration resulted in significantly greater dysphoria and somatic effects (LSD), sedation (PCAG), and both alcohol sedation and euphoria compared to placebo. Notably, cannabis by itself resulted in significantly greater euphoria compared to alcohol and cannabis combined in this study.

The Biphasic Alcohol Effects Scale and Drug Effects Questionnaire

Only one study has examined the impact of co-administration of alcohol and cannabis on subscales of the BAES. In this study, a small sample of young adults (N=11) consumed either a moderate (0.2g/kg) or low (0.1g/kg) dose of alcohol with an oral cannabis capsule containing 2.5mg THC (dronabinol). The within-person interaction of cannabis with these doses of alcohol did not result in a significant change from baseline on BAES measures of stimulation and sedation (Ballard and de Wit, 2011). This study also assessed subjective drug effects using the DEQ and found that mean change scores of ‘want more’ significantly decrease post-administration of a moderate dose of alcohol and oral THC. Previous research shows that alcohol administered alone results in significant increases in DEQ ratings of ‘drug effect’ and ‘want more’ (King et al., 2011). Taken together, the authors suggest findings may reflect cannabis’ potential to mitigate the effects of alcohol on the desire to want more of each substance. In a separate sample, using a within-subject experimental design, alcohol combined with a fixed paradigm of smoked cannabis (13mg THC) significantly increases ratings of ‘drug effect’ compared to alcohol-only, cannabis-only, and placebo (Ronen et al., 2010). In this case, the authors suggest that alcohol and cannabis combined produces an additive effect. However, it is worth noting that reviews and discussions within the literature offer mixed findings on whether cannabis serves as a substitute for or a complement to alcohol (Gunn et al., 2022b). Thus, inconsistencies across studies may be the result of variations in cannabis administration (oral vs. smoked), dosage, and administration paradigms (ad-libitum vs. fixed smoking procedure, order of substance administration).

Visual Analog Scale

Subjective drug effects are frequently evaluated through the use of VAS ratings. Research shows that the administration of active cannabis and alcohol produces more robust VAS ratings of subjective drug effects compared to placebo conditions (Cooper and Haney, 2014). However, findings from co-administration studies employing VAS measures are inconsistent. Some of the earliest work examining the effects of co-administration on measures of alcohol and cannabis intoxication, compared to each substance alone, results in null findings (Chait and Perry, 1994; Perez-Reyes et al., 1988). Subsequent research, in a separate sample (N=11, 5 women) of individuals who occasionally use cannabis (2-10 times in lifetime, no more than 4 times in past month), also found that the within-person interaction of alcohol (0.1 g/kg and 0.20 g/kg) and oral cannabis (2.5 mg dronabinol capsule) did not result in a significant change from baseline on VAS ratings such as ‘sleepy’, ‘hungry’, ‘stimulated’, ‘anxious’, ‘sedated’, ‘elated’, and ‘nauseated’(Ballard and de Wit, 2011). However, several studies present contrasting evidence, providing support for the hypothesized additive and synergistic effects of the SAM use (Hartman et al., 2016; Lukas and Orozco, 2001; Ronen et al., 2010).

In a sample of men (N=22) who use alcohol and cannabis (1.5-2 joints per week and 4-8 beers per week), a fixed administration of moderate dose alcohol (0.7 g/kg) and low dose cannabis cigarettes (1.26% THC) resulted in a longer duration of euphoric (‘good’) effects, with changes occurring within 0 to 15 minutes post smoking onset and persisting up to 30-40 minutes, compared to the co-administration of low dose alcohol (0.35 g/kg) and low dose cannabis (Lukas and Orozco, 2001). However, the combination of low dose alcohol and moderate dose cannabis (2.53% THC) in this study resulted in a longer duration of euphoric (‘good’) effects compared to the placebo condition and the co-administration of moderate dose alcohol and cannabis condition. Participants in this study did not report any dysphoric (‘bad’) effects from the co-administration of alcohol and cannabis (Lukas and Orozco, 2001). Ronen and colleagues show that fixed administration paradigms of alcohol (target level 0.05% BAC) with cannabis (13mg THC) results in significantly higher VAS ratings of ‘sedation’ compared to placebo, alcohol-only, and cannabis-only (Ronen et al., 2010). Conversely, in a separate sample of individuals who heavily used cannabis (>4x/week), alcohol and THC combined show comparable levels of alcohol intoxication compared to alcohol alone (Ramaekers et al., 2011). Among individuals who self-reported an average cannabis consumption of ≥1x/3months but ≤3days/week over the past 3 months and self-reported “light” or “moderate” alcohol consumption (but not more than 3-4 servings in a typical drinking occasion) according to the Quantity-Frequency-Variable (QFV) scale (Sobell et al., 1995), VAS ratings of ‘high’, ‘good effect’, ‘stimulated’, ‘stoned’, and ‘sedated’ persisted longer following ad-libitum vaporized cannabis (2.9% THC; 6.7% THC) when combined with alcohol (90% grain alcohol to ~0.065% peak BrAC), compared to cannabis alone (Hartman et al., 2016). Findings suggest the prolonged duration of cannabis’ effects is dose-dependent and based on the type of alcohol consumed, which provides partial support for the hypothesized additive and synergistic effects of SAM use.

Recent studies among individuals who use cannabis at least weekly and engage in heavy episodic drinking, show that the co-administration of alcohol (80mg/dL, target BrAC) and smoked cannabis (12.5% THC) results in significant increases on a number of VAS measures compared to alcohol and cannabis alone. These measures include ‘drug effect’, ‘like drug effect’, ‘good effect’, ‘bad effect’, ‘rush’, ‘dizzy’, ‘drunk’, ‘exhilarated’, ‘drowsy’, and ‘nauseated’ (Fares et al., 2022). Co-administration also led to a significant increase in the VAS measure of ‘high’, although this increase was not significantly different from cannabis alone. In a separate study of 18 adults, the co-administration of intravenous alcohol (0.04% BAC) and oral cannabis (10mg dronabinol capsule) resulted in greater VAS ratings of ‘high’, ‘buzzed’, ‘tired’, ‘drowsy’, ‘mellow’, and ‘hungry’ (Schnakenberg Martin et al., 2023). The substantial variability in the combined effects of alcohol and cannabis on VAS ratings of subjective drug effects underscores the complex nature of combining these substances.

While laboratory studies provide important insight regarding the acute effects of co-use on subjective drug effects, several factors should be considered when interpreting results. An individual’s history of substance use, including frequency, quantity, and duration of use may influence simultaneous use effects due to the potential development of tolerance among those who heavily use substances. Given the small and homogenous samples in these studies (N<30, predominantly male), results may not generalize to more heterogeneous samples or individuals with more frequent and/or heavier alcohol and cannabis. Mixed findings may also be a result of methodological differences across studies such as method of alcohol (e.g., intravenous vs. oral) and cannabis (e.g., smoked, vaporized, capsule) administration, alcohol and cannabis dosage, and administration paradigms (e.g., ad libitum and/or fixed paradigm). Research studies show that cannabis pharmacokinetics vary by method of administration, such that smoked and vaporized cannabis results in peak THC and CBD plasma concentration levels within 10 minutes of administration and oral cannabis (e.g., edibles) results in peak THC and CBD plasma concentration levels within 90-120 minutes (Lucas et al., 2018; Spindle et al., 2020, 2019). The difference in onset and intensity of cannabinoid plasma concentrations may influence the timing and perception of subjective drug effects. Future studies should consider adopting a systematic approach to varying doses, order and methods of substance administration, and recruitment and examination of diverse samples (e.g., sex-balanced, occasional/frequent use, AUD/CUD).

Summary of Experimental Findings

CBD does not appear to impact the subjective effects of alcohol; however, this research is limited and future studies need to be conducted to replicate and extend the existing findings. Early co-administration studies of THC and alcohol, using measures such as the POMS, failed to show significant effects on mood. Subsequent studies, albeit with relatively small sample sizes, suggest that the combined effects of THC and alcohol tend to be additive, and in some cases, may counteract each other's effects. However, recent research with larger samples reveal significant changes in tension-anxiety and confusion when alcohol and THC are co-administered, suggesting a more complex interaction. Only one study has examined the effects of THC and alcohol co-administration on measures of stimulation and sedation, using the BAES, and did not observe significant effects. However, in this same study, a decrease in the desire to ‘want more’, as measured by the DEQ, was observed, suggesting that THC may mitigate the desire for additional alcohol or cannabis. The use of VAS ratings to assess subjective drug effects also yields mixed results. Some studies found no significant changes in VAS subjective effects when THC and alcohol were combined, while others reported significant increases in effects. Overall, the inconsistent findings in the literature may be attributed to variations in sample sizes, methodological differences (e.g., dosages, administration methods, assessment measure), and participant characteristics (e.g., frequency of alcohol and cannabis use).

Naturalistic Examination of Simultaneous Alcohol and Cannabis Use.

While studies demonstrate that the use of alcohol and cannabis alone are associated with changes in subjective drug effects (Zeiger et al., 2012), there is a lack of research on SAM use and subjective drug effects in real-world contexts.

The Subjective High Assessment Scale

Only one cross-sectional study has examined the effects of SAM use on subjective drug effects. In a large (N=315) sample of young adults, who reported at least one occasion of lifetime SAM use, subjective drug effects were assessed using the SHAS-7. This study shows that the perceived effects of feeling ‘drunk’ were greater during SAM use compared to the use of alcohol alone (Lee et al., 2017). However, perceived cannabis effects (i.e., ‘high’, ‘cannabis effects’) were greater for cannabis use alone compared to SAM use. Although the authors suggest findings support enhanced experiences of subjective effects when alcohol and cannabis are simultaneously used, reports of substance use and resulting subjective effects were assessed retrospectively across the participant’s lifetime and based on “typical” use. When recalling subjective drug effects during a “typical” use occasion, individuals may rely on cognitive heuristics that represent the most intense and/or proximate aspects of their substance use experience. Recent work shows individuals tend to overemphasize their peak (best/worst) and end (current) mood states, resulting in peak-end bias. This bias refers to the tendency for the most intense and proximate aspects of an experience to disproportionately influence our memory (Horwitz et al., 2023). Retrospective reports of subjective drug effects, in this manner, may be susceptible to the influence of a nonrepresentative period of time (e.g., past month) that may not accurately reflect patterns of SAM use and experiences that occur in daily life.

Subjective Effects of Alcohol Scale

While several studies have examined the effects of SAM use on consequences and consumption (Gunn et al., 2022b, 2021; Stevens et al., 2021), only three studies have examined how SAM use may impact subjective intoxication in daily life. In a sample of young adults who engaged in past-month solitary drinking, social drinking, and heavy-episodic drinking (4/5 drinks women/men in a night), and reported at least one instance of same-day alcohol and cannabis co-use, SAM use was associated with significant increases in momentary and day-level high arousal positive/rewarding, low arousal positive/relaxing, and low arousal negative/impairing effects, as measured via the SEAS, compared to alcohol-only moments/days (Waddell et al., 2023a). Further, more frequent simultaneous use was associated with higher between-person levels of high/low arousal positive effects.

Visual Analog Scale

Young adults who engaged in heavy episodic drinking (N=154, 57.8% women), and at least one occasion of past-month SAM use, reported no differences in subjective intoxication when 217 SAM use days were compared to 377 alcohol-only and 368 cannabis-only days (Linden-Carmichael et al., 2020). Notably, individuals in this study reported on patterns of substance use and related experiences from the previous day, which may introduce some degree of recall bias. In contrast to this study, in a separate sample of young adult college students (N=341), reporting past month SAM use, subjective intoxication was significantly greater on 2017 SAM use days relative to 2073 alcohol-only and 3909 cannabis-only days (Sokolovsky et al., 2020). Laboratory studies indicate that subjective intoxication peaks within 10 to 30 minutes post administration of alcohol and cannabis, returning to baseline levels within three hours (Hartman et al., 2016). However, in studies examining the effects of SAM use at the day-level (Linden-Carmichael et al., 2020; Sokolovsky et al., 2020), reports of intoxication were collected either once daily or aggregated across a specific day, resulting in a single time-point for analysis. Thus, it is unclear which specific reference point of intoxication (e.g., peak, average, end) individuals are referring to when reporting on their substance use experience.

Summary of Naturalistic Findings

Only one study has examined the effects of SAM use on the domains of valence and arousal using multiple levels of assessment (e.g., moment, day, person) such that findings revealed a similar pattern of effects for high/low arousal positive and low arousal negative effects. Moreover, naturalistic studies do not encompass a wide range of subjective drug effects (e.g., ‘stimulation’, ‘sedation’, ‘good effects’, ‘bad effects’, ‘liking the effects’, ‘want more’) which are common measures of abuse liability in experimental settings. This makes it challenging to determine if the effects of SAM use in real-world settings are similar to the effects observed in laboratory studies. Future research should consider implementing more intensive repeated assessment [e.g., ecological momentary assessment (EMA)] of substance use and experiences to clarify the effects of SAM use on subjective drug effects at the within- and between-person levels.

Implications for Future Research

This review underscores the need for continued research on the effects of SAM use on subjective drug effects, particularly as this type of use pattern of alcohol and cannabis becomes increasingly common among young adults. Future research should consider expanding on the existing literature in several ways. First, the experimental studies reviewed had relatively small and homogenous samples. This may limit the ability to identify significant effects due to the potential for inadequate statistical power. Notably, while the majority of the studies in this review focus on the effects of SAM use among young adult college students, some studies do include adult populations. This may impact the conclusions that may be drawn from these studies. Factors such as motivation and coping strategies, contextual settings, risk and protective factors, and health-related conditions may differ across age groups and influence subjective responses related to SAM use. Future studies should recruit larger, more diverse, and representative samples, including consideration of sex- and age-balanced samples, participants with varying levels of substance use and SAM use, and individuals with and without AUD or CUD. Furthermore, there is a need to examine these considerations more specifically across various co-use patterns. This approach will enhance the generalizability of research findings to a broader and more inclusive population.

There has been substantial diversification in methods of cannabis administration. As illustrated, studies administer cannabis through smoked, vaporized, and oral procedures which may contribute to discrepant outcomes concerning subjective drug effects. Prior research shows that each method of cannabis consumption may represent a distinct route of administration on subjective drug effects (Cooper and Haney, 2009). As new trends and products related to alcohol and cannabis use emerge (e.g., high-potency, edibles, cannabis-infused beverages, sublingual), researchers should consider examining how various methods of SAM use influence subjective drug effects using qualitative, experimental, and naturalistic examination. Furthermore, changes in subjective drug effects may be dose-dependent. When alcohol and cannabis are used together, the pharmacological effects of each substance may interact in complex ways. Research shows blood levels of THC are significantly higher in the presence of alcohol (Hartman et al., 2016), which may, in part, explain observed changes in subjective responses following co-administration. No prior laboratory work has directly examined the effect of order of alcohol and cannabis administration, with the exception of Karoly and colleagues’ (Karoly et al., 2022) recent proposal to examine order effects on objective and subjective intoxication via a mobile laboratory study. To our knowledge, no study has examined the effects of order of substance use on subjective drug effects in a naturalistic setting. Popular lore in the cannabis culture surrounding the effects of order of cannabis use with alcohol persist, and the lack of empirical research in this area underscores the need for more rigorous scientific investigations.

Lastly, research focused on SAM use has both clinical and public policy implications. Findings from this research can contribute to targeted public health education and intervention efforts which include raising awareness about the risks of SAM use, potential interaction effects of alcohol and cannabis, and harm reduction strategies aimed at decreasing SAM use across age groups. Further, clinicians can incorporate knowledge about SAM use patterns into screening and assessment tools. That is, if an individual is engaging in specific SAM use behaviors, clinicians can draw upon the existing literature to implement targeted interventions and treatment plans to address both alcohol and cannabis use. Given the common perceptions and beliefs surrounding the complementary and synergistic effects of alcohol and cannabis use (i.e., “cross-faded” effects), SAM use continues to be a complex and evolving phenomenon. By better understanding how individuals respond to the combination of alcohol and cannabis, findings may be used to inform harm reduction strategies that provide empirical support related to the effects of SAM use in order for young adults to make informed decisions related to their overall use patterns.

Figure 1.

This narrative review focuses on the effects of the simultaneous use of alcohol and cannabis on subjective drug effects across methodologies (e.g., qualitative, laboratory experiments, naturalistic settings). While prior research has delineated the effects of alcohol and cannabis alone on subjective drug effects, there is a lack of clarity on how simultaneously using these substances may impact subjective experiences across methodologies. This review will provide an overview of the existing findings, address inconsistencies in the literature, highlight how methodological limitations across studies may be contributing to a lack of clarity on SAM use effects, and summarize key considerations in the implementation of future research.