Evidence synthesis – Patterns and motivations of polysubstance use: a rapid review of the qualitative evidence

Abstract

Introduction: Polysubstance use—the use of substances at the same time or close in time—is a common practice among people who use drugs. The recent rise in mortality and overdose associated with polysubstance use makes understanding current motivations underlying this pattern critical. The objective of this review was to synthesize current knowledge of the reasons for combining substances in a single defined episode of drug use.

Methods: We conducted a rapid review of the literature to identify empirical studies describing patterns and/or motivations for polysubstance use. Included studies were published between 2010 and 2021 and identified using MEDLINE, Embase, PsycINFO and Google Scholar.

Results: We included 13 qualitative or mixed-method studies in our analysis. Substances were combined sequentially to alleviate withdrawal symptoms or prolong a state of euphoria (“high”). Simultaneous use was motivated by an intention to counteract or balance the effect(s) of a substance with those of another, enhance a high or reduce overall use, and to mimic the effect of another unavailable or more expensive substance. Self-medication for a pre-existing condition was also the intention behind sequential or simultaneous use.

Conclusion: Polysubstance use is often motivated by a desire to improve the experience based on expected effects of combinations. A better understanding of the reasons underlying substance combination are needed to mitigate the impact of the current overdose crisis.

Keywords: polysubstance use, polydrug use, misuse, drug combination, co-use, co-ingestion, rapid review

Introduction

Polysubstance use, the consumption of more than one substance close in time, with overlapping effects,^{Footnote 1Footnote 2} is increasingly recognized as an urgent public health issue.^{Footnote 3Footnote 4Footnote 5Footnote 6} The co-involvement of stimulants, benzodiazepines and alcohol increases the risk of acute opioid toxicity^{Footnote 7} and has been identified as one of the key drivers in the rise in opioid-related mortality in North America.^{Footnote 3Footnote 4Footnote 5Footnote 6} In Canada, 22 828 apparent opioid toxicity deaths were recorded between January 2016 and March 2021.^{Footnote 8} Although it is most prevalent among people with problematic use,^{Footnote 6Footnote 9Footnote 10Footnote 11} polysubstance use is far-reaching and occurs across populations and age groups.^{Footnote 12Footnote 13Footnote 14Footnote 15Footnote 16}

Overdose death rates have risen rapidly since the onset of the COVID-19 pandemic.^{Footnote 8} Between April and September 2020, in the 6 months after the implementation of COVID-19 prevention measures, there were 3351 apparent opioid toxicity deaths in Canada, representing a 74% increase over the previous 6 months (1923 deaths between October 2019 and March 2020).^{Footnote 8} Recent evidence suggests that physical distancing measures have contributed to this situation by reducing the availability of treatment and harm reduction services for people who use substances.^{Footnote 17} Although the literature on polysubstance use in the context of COVID-19 is still nascent, findings from recent reports also suggest that self-medication and the effects of abstinence from no longer accessible drugs has resulted in an increase in the number of substances used simultaneously.^{Footnote 18} This trend is a concern given that it contributes to multiple dependencies,^{Footnote 19Footnote 20Footnote 21} especially when substances are consumed to mitigate a negative symptom, for example, to manage pain.^{Footnote 22}

Studies have shown that people combine substances with the intention of minimizing harm, reducing negative symptoms, increasing pleasurable sensations and enhancing overall experience, despite the risk of acute toxicity inherent to polysubstance use.^{Footnote 23} Qualitative and mixed-method studies have reported various motivators of polysubstance use in specific populations,^{Footnote 24Footnote 25Footnote 26Footnote 27Footnote 28} but a comprehensive synthesis of the literature is missing. As studies relying on qualitative data tend to be small, a synthesis of the literature could provide a broader and more complete picture of polysubstance use motivations in the population, help identify common and less common motivating factors, and inform substance-use intervention and prevention programs and policies.

In this review of qualitative evidence, we aim to summarize the current state of knowledge on the way people choose to combine substances in a single episode, either at the same time or sequentially, to achieve desired effects.

Methods

Search strategy

We developed this review using the methods described in the Rapid Review Guidebook.^{Footnote 24}

An electronic database search strategy was developed with a librarian based on a pre-specified protocol (available from the authors on request). We searched MEDLINE, Embase and PsycINFO databases for peer-reviewed studies published between January 2010 and March 2021. We identified grey literature by searching the Google and Google Scholar databases for governmental reports and webpages of the Organisation for Economic Co-operation (OECD) and of OECD member countries. An ancestry search of all the references cited by all included peer-reviewed articles and a manual search in Google Scholar for key concepts such as pattern of polysubstance use were carried out to capture relevant studies that may not have been indexed in the searched databases.

Studies were eligible for inclusion if they (1) reported on the pattern or motivation of polysubstance use; (2) were qualitative or mixed methods using original data; (3) were conducted in OECD countries; and (4) were written in French or in English. There were no restrictions on study population or context/setting.

Studies were excluded if they (1) reported motivations only for alcohol and/or cannabis and/or tobacco or a combination of these with a non-psychoactive substance because the focus was on combinations associated with more severe problematic use;^{Footnote 25} (2) reported no specific combination(s); (3) relied on data collected before 2005, to capture recent patterns of use; (4) described the probability of combining substances with no mention of motivations; or (5) did not specify a time period of use or described the use as taking place for a period longer than 24 hours.

Study selection and data collection

Two reviewers (MBF, CL) independently screened titles and abstracts and retrieved potentially relevant studies for full-text review. Three reviewers (MBF, GC, GG) independently extracted data from the included studies. Any discrepancies between reviewers at screening and full-text review were resolved via consensus. For all included publications, the study country, objective(s), population, sample size, data collection method, years of data collection, basic demographic data of study participants including age, sex, substances under study and combinations of substances and or classes were extracted. Motivations for combining different substances, and patterns of substance use (simultaneous or sequential), were coded.

Quality appraisal

Three reviewers (MBF, GC, GG) independently assessed the quality of included studies using the Mixed Methods Appraisal Tool (MMAT).^{Footnote 26Footnote 27} This tool has been developed and validated to critically appraise the methodological quality of different study designs. The MMAT uses five questions to assess the appropriateness of the study design for the research question, the potential bias and the quality of measurements and analyses, according to design.

Based on “yes,” “no” or “can’t tell” answers, a five-point quality score was created, assigning one point for each “yes” response. Studies were considered good quality (≥4 “yes” answers); moderate quality (3 “yes” answers); or poor quality (≤2 “yes” answers). Disagreements between reviewers were resolved if any of their answers to the five questions described in the MMAT tool differed. Consensus was reached through discussion between two reviewers, followed by discussions with a third if the disagreement persisted.

No studies were excluded based on their quality. (Details of the complete quality appraisal results of all included studies are available from the authors on request).

Data analysis

We extracted qualitative data on polysubstance use, including the specific substances combined and their class (stimulants, depressant, dissociative, psychedelics, etc.). We defined polysubstance use as the consumption of at least two substances at the same time (simultaneous pattern) or taken one after another within a 24-hour period (sequential pattern).

We carried out a thematic content analysis to identify the motivations and patterns of use. We coded qualitative information using a predetermined list of motivations extracted from a published review,^{Footnote 10} allowing for more to emerge. Once the list of motivations stabilized, two reviewers (either MBF and CL, or MBF and GC) coded the verbatims separately and then compared their results. A single quote could be coded under more than one motivation. If the reviewers disagreed as to the motivation to ascribe, they resolved the disagreement through discussion, with a third reviewer joining the discussion if the disagreement persisted.

Results

Study selection and characteristics

The initial electronic database search yielded 814 studies, and the grey literature search 37 records. After the removal of duplicates (n = 8) and ineligible records on the basis of their title and abstract (n = 453), 353 manuscripts underwent full-text review. Of these, 8 studies^{Footnote 28Footnote 29Footnote 30Footnote 31Footnote 32Footnote 33Footnote 34Footnote 35} were included in the review (Figure 1). Five more peer-reviewed studies were added through the ancestry and manual searches.^{Footnote 14Footnote 36Footnote 37Footnote 38Footnote 39}

Figure 1 - Text description

This figure details the data identification, selection and extraction process. For peer-reviewed literature, 814 records were identified through database search. 8 of these records were duplicates. Of the remaining 806 abstracts reviewed, 453 were irrelevant. After the full text review of the remaining 353 records, 345 were excluded for the following reasons: 171 were irrelevant, 29 were not original studies, 20 were not qualitative or mixed, 20 were published before 2010 (data before 2005), 79 had no described definition/combination/motivation, 7 had only toxicological analyses, 6 articles were not found, 4 were conducted in non-OECD countries, 3 had incomplete data, 4 were duplication, 1 was a case report, and 1 was written in a foreign language. For grey literature, 37 records were identified through grey literature search. Of these 37 records, there were no duplicates and only 1 irrelevant record. Following a full-text review of the 36 remaining records, 36 were excluded for the following reasons. 16 were not an original study, 14 had no description of polysubstance, 1 was conducted in a non-OECD country, 1 was published before 2010 (data before 2005), 3 were duplicates, and 1 only had toxicological analyses. No grey literature records were included. To supplement the 8 included peer-reviewed records, an ancestry and manual search of peer reviewed studies provided 5 more records. The total included records is 13.

Eleven of the included studies were conducted in North America^{Footnote 14Footnote 28Footnote 29Footnote 30Footnote 32Footnote 34Footnote 36Footnote 37Footnote 38Footnote 39Footnote 40} and two in Europe.^{Footnote 33Footnote 35} Six were qualitative and 7 were mixed methods studies. The characteristics of included studies are summarized in Table 1.

We classified nine of the studies as high quality. Four mixed-methods studies were considered moderate quality, either because they did not provide a clear rationale for using mixed methods or because the quality of the quantitative and/or qualitative research methods could not be assessed based on the reported information.

The median number of participants in the selected studies was 45, with the actual number between 11 and 13 521. The study population was categorized into one of the six following groups: people who attend parties and raves and go to bars; people attracted to the same sex; people attending academic or training institutions; people who inject substances and/or are street involved and/or experiencing homelessness; and people who use substances not otherwise specified.

Ten of the 13 studies were conducted with street-based or socially marginalized populations including people who inject drugs, use harm reduction services or are experiencing homelessness.^{Footnote 14Footnote 29Footnote 30Footnote 32Footnote 33Footnote 35Footnote 37Footnote 38Footnote 39Footnote 40}  The age range varied across the studies, with the overall range 18 to 60 years.

One study examined the reasons for polysubstance use in a population of university students (median of 21 years of age)^{Footnote 28}; one examined the reasons for polysubstance use among people attracted to the same sex (median of 23 years of age)^{Footnote 36}; and one examined the reasons for polysubstance use among people who discuss substance use in online forums (mean of 23 years of age)^{Footnote 34}. Most of the study participants (50–100%) identified as male.

Patterns and motivations for combining substances

The 13 studies included in this rapid review reported a total of 41 different combinations of substances and the motivations for combining substances (Table 2).

Table 2. Specific motivations for combining substances identified in qualitative or mixed-method studies (N = 13)

Motivation	Combination of classes and substances		Description of specific motivations according to specific substances combined
	Class + (specific substance)	Class + (specific substance)
Sequential use (proximal time)
Alleviate withdrawal symptoms	Opioid (heroin)	Opioid (Rx opioids)	To ease pain when coming down from heroinFootnote 31Footnote 37
	Opioid (prescribed)	Alcohol	To induce sleep after using an opioidFootnote 30
	Stimulant (mephedrone)	Opioid (heroin and methadone)	To come down off a stimulantFootnote 35
	Stimulant (cocaine)	Antidepressant (trazodone)	To induce sleep after using a stimulantFootnote 32
		Antipsychotic (quetiapine)	To alleviate distress and induce sleep after using a stimulantFootnote 32Footnote 36
		Benzodiazepine (clonazepam or lorazepam) with or without alcohol	To cope with anxiety and paranoia, induce sleep and avoid cravings (“jonesing”) after using a stimulantFootnote 32Footnote 37
		Gabapentinoid (pregabalin)	To reduce anxiety induced by a stimulantFootnote 32
		Stimulant (dexamfetamine)	To come down, avoid “crashing” after the use of a stimulantFootnote 28
		Opioid (methadone)	To calm down after using a stimulantFootnote 33
	Stimulant (methamphetamine)	Benzodiazepine (alprazolam) with or without alcohol	To induce sleep, to calm down and prevent hallucinations after using a stimulantFootnote 32
		Stimulant (dexamfetamine)	To maintain functioning after a prolonged session of stimulant useFootnote 36
		Opioids (NS)	To alleviate withdrawal symptomsFootnote 29 and to reduce paranoia induced by a stimulantFootnote 30
	Stimulant (Adderal or MDMA)	Benzodiazepine (alprazolam)	To induce sleep after using a stimulantFootnote 39
	Stimulant (dexamfetamine)	Cannabinoid (cannabis)	To relax, numb physical exhaustion after using a stimulant. To mentally signifying the end of a productive period or the beginning of recreational timeFootnote 28
		Alcohol	To achieve a level of soberness after using alcoholFootnote 36
		Benzodiazepine (alprazolam)	To induce sleep after using a stimulantFootnote 36
Prolong a high	Stimulant (cocaine)	Opioid (hydromorphone)	To create a pattern of successive stimulation and sedationFootnote 14Footnote 42
Simultaneous use
Balance effects	Opioid (heroin)	Benzodiazepine (clonazepam)	To avoid being aggravated easily by noise and reduce anxietyFootnote 31
	Stimulant (cocaine)	Opioid (heroin or dilaudid)	To avoid negative experiences (“bad trips”), overpowering sensationsFootnote 33; to avoid feeling drowsy (“nodding”) when using an opioidFootnote 38
		Opioid (heroin) + Opioid (mephedrone)	To avoid overpowering sensationFootnote 35
		Methamphetamine +/− opioid	To avoid overpowering sensationFootnote 29Footnote 30
	Rx stimulant (dexamfetamine)	Alcohol	To calm downFootnote 28
		Cannabis	To calm down and to increase appetiteFootnote 28
	Stimulant (methamphetamine)	Opioid	To provide energy to offset the sedation from opioids, to calm down after using the stimulantFootnote 30
		Opioid (heroin)	To avoid overpowering sensationFootnote 30
		Rx opioids	To provide energy to offset the sedation from opioids, or to calm down after using the stimulantFootnote 30
		Alcohol	To avoid overpowering sensationFootnote 30
Counteract effects	Stimulant (methamphetamine)	Erectile dysfunction Rx (Cialis, Viagra)	To counteract the effect of a stimulant on sexual performanceFootnote 36
	Rx stimulant (dexamfetamine)	Cannabis	To counteract the effect of the stimulant and restore appetiteFootnote 28
Enhance a high	Opioid (heroin)	Benzodiazepine (clonazepam)	To enhance the effect of the opioidFootnote 31Footnote 32
		Opioid (oxycodone)	To enhance the effect and achieve the desired high with low quality drugFootnote 31
	Opioid (Rx opioid)	Cannabis	To accentuate or enhance the effects of cannabisFootnote 37
	Stimulant (cocaine)	Stimulant (methylphenidate)	To enhance the effect of the stimulantFootnote 32
	Stimulant (dexamfetamine)	Stimulant (clonidine)	To enhance the effect of the stimulantFootnote 32
		Stimulant (caffeine)	To enhance the effect of the stimulantFootnote 28
	Stimulant (methamphetamine)	Opioid	To increase enjoyment of effectFootnote 29
		Rx opioid	To enhance the effect of the stimulantFootnote 30
		CNS depressant (GHB), Dissociative (ketamine)	To enhance sexual experience or self-discovery experiencesFootnote 14
	Cocaine	Opioid (NS)	To maximize the effect of one drug or the otherFootnote 38
Reduce overall use	Opioid (Rx opioid)	Alcohol	To achieve the same effect while reducing overall use and harm related to alcohol useFootnote 39
Mimic the effect of another substance	Opioid (methadone)	Benzodiazepine	To mimic the effect of heroinFootnote 32
Temporality of use not specified
Self-medicate	Opioid (heroin)	Rx opioid	To self-medicate painFootnote 14
Abbreviations: CNS, central nervous system; GHB, gamma-hydroxybutyrate; MDMA, methylenedioxymethamphetamine (ecstasy); NS, not specified; Rx, prescribed medication. Note: We use the colloquial expression “high” to mean a state of euphoria induced by the taking of the drug(s).

We found eight motivations for which we described the temporal patterns of use (simultaneous or sequential) when information was available. Excerpts of quotes from the original studies are duplicated here to better illustrate individuals’ motivations for combining substances.

Sequential use

Sequential use refers to the consumption of a substance after the peak effect of another substance. People reported using substances sequentially to alleviate withdrawal symptoms or to prolong a state of euphoria, or “high.”

Alleviate withdrawal symptoms

The most frequently reported combinations of substances involve a stimulant with a depressant (e.g. benzodiazepine, alcohol), cannabis or an opioid to either calm down, induce sleep, alleviate anxiety or distress or avoid drug cravings^{Footnote 28Footnote 32Footnote 35Footnote 37Footnote 39} produced by the stimulant.

“Sometimes when you do cocaine, or you get really wired up on the Oxys, we need something to come down, and we would take that Xanax to come down or get some sleep because sometimes in the process of doing these drugs you forget to sleep for a couple of days, and then finally you’ve got to say, ‘Okay, it’s time to sleep.’”^{Footnote 37}

Studies reported people using substances within the same class of effect to ease off the effects of the drug. For example, a prescribed stimulant (dexamfetamine) was used to maintain normal functioning after a prolonged session of methamphetamine^{Footnote 36} or cocaine^{Footnote 28}. Similarly, oxycodone was used to ease the pain of heroin withdrawal.^{Footnote 37Footnote 40}

“I kind of like to ride like a stimulant wave, it’s very typical for me to after doing crystal all weekend to just do Adderall, to get through the day. Because, again, you’re not kind of cranky, you’re still up and you’re still awake, and you’re not tired, and you’re able to do super-human things by just keeping going.”^{Footnote 36}

“… Hey, if you’re sick, what will help is the Percocet. (…) the withdrawals make me feel really shitty. You know? But the Percocet, it kind of takes away all that. So that’s why I use it…I only use it because I will go through withdrawals from the heroin, so I use the Percocet to ease the pain when I can’t get heroin.”^{Footnote 37}

Prolong a high

The pattern of stimulation sedation can take place in a single day or for longer periods (several days) with stimulants and opioids to prolong a high.^{Footnote 14Footnote 38}

“I would smoke crack and use heroin or fentanyl, what we call landing gear, to come back down. And once you get down, then you’ll want to take another hit [of crack] to go back up, and it’s just like a cat chasing its tail. It never ends. Go up just to come down, then go up [again].”^{Footnote 14}

Simultaneous use

Simultaneous use is defined here as the consumption of two or more substances at the same time or close in time. The intention of simultaneous use is usually to balance or counteract the effects of one substance by using another substance, to enhance a high, to reduce overall use or to mimic the effect of another substance.

Balance effects

Substances with opposing psychoactive effects were used simultaneously to achieve a desired mental state or to temper undesirable effects. For example, heroin is used to avoid experiencing negative overpowering feelings when using a stimulant.^{Footnote 33}

“... you no longer think about hallucinations, paranoia, you don’t go through a bad trip, it [simultaneous use of heroin and crack cocaine] is the best thing to reduce the effect.”^{Footnote 33}

Similarly, a stimulant is used to avoid feeling drowsy when using an opioid or as a depressant.^{Footnote 30Footnote 38}

“I’ll take Adderall mainly when I go to the clubs. At nighttime when I’m too drunk, I’ll take the Adderall to straighten me up a little bit, open my eyes, be more attentive.”^{Footnote 36}

Counteract effects

Substances with complementary effects can be used simultaneously to counteract undesired effects. For example, erectile dysfunction medication is used to counteract the effect of methamphetamine on sexual performance,^{Footnote 36} and cannabis is used to increase appetite when using a stimulant.^{Footnote 28}

“I smoke the weed to control [the Adderall]. If I get too jittery—too uppity—and I’m grinding [my teeth] way too much, okay, I need to smoke to calm down some, and let myself know I got to eat something.”^{Footnote 28}

Enhance a high

Motivations for polysubstance use included combining drugs to create synergistic psychoactive effects with the intent to potentiate or enhance the effects of another substance. Often, stimulants are used in combination to increase a high.^{Footnote 28Footnote 32} People also reported using benzodiazepines^{Footnote 31Footnote 32} or prescription opioids^{Footnote 31} with heroin for the same purpose. Opioids and stimulants were also used in combination to maximize the effect of one drug or the other and create a synergy.^{Footnote 38} Substances may also be combined with the specific purpose of enhancing the effect of a low quality drug to achieve the desired high.

“For crappy dope, I’m gonna try to get some Oxys for free, take those, and do a shot of dope. Or, I’ll take a Percocet, start feeling that, and then do a shot of dope, which just intensifies it.”^{Footnote 31}

Stimulants are combined simultaneously with GHB (gamma-hydroxybutyrate) and ketamine for added pleasure and to enhance sexual experiences or self-discovery.^{Footnote 14}

“But then [if] you want to go voyaging off into the universe, do a shot of crystal [crystal meth] and special K [ketamine] in the same shot. It’s amazing … I don’t know how to explain it. I feel like I’ve learned a lot about life in those kinds of experiences.”^{Footnote 14}

Reduce overall use

Substances can be used simultaneously as a harm reduction strategy to decrease substance consumption. For example, alcohol is used with an opioid to achieve the same effect of alcohol while reducing overall intake.^{Footnote 39}

“It’s usually like, ‘Oh, we’re going out to the bar, OK, I’ll take half a Vicodin and have a couple of drinks, because it makes it that much more intense without having to consume as much.’ [That] is my approach to it. I can go out and have two drinks and take half the Vicodin and feel better than going and having four or five drinks that night.”^{Footnote 39}

Mimic the effect of another substance

Substances are mixed to help users achieve a desired effect if a preferred substance is not available or only available at a higher price. For instance, participants reported simultaneously using benzodiazepines and methadone to mimic the effects of heroin when that drug is not available.^{Footnote 32}

“When I take methadone and benzos I nod [laughs] … Nodding is when you are high on heroin. Methadone and benzos make you nod. That’s why some doctors don’t want to prescribe both. It makes the effect of heroin. Methadone and benzos make you high like heroin.”^{Footnote 32}

Pattern not specified

Self-medicate

Self-medication for poorly managed physical or mental health conditions or to alleviate pain was another common reason for using more than one substance. For instance, a participant described using Suboxone for pain and also self-medicating with a benzodiazepine and Ritalin to cope with a pre-existing condition:

“[I currently use] Suboxone. I also like to use Xanax [benzodiazepine], it calms me down. The Concerta, the Ritalin [prescription stimulants], gives me energy. I mean, of course, the Suboxone, takes away all the [pain]. ‘Cause I also have chronic pain, and it does help, and that’s mostly (…) just to make it through the day and not be in so much pain.”^{Footnote 14}

Complex behaviour and superimposed motivations

During a single episode of polysubstance use, there may be multiple motivations that guide the choices of people who use drugs, and drugs may be used both sequentially and simultaneously to meet these goals. For example, the use of alcohol and cannabis often constitute the baseline on which to build the experience, which can then be followed by a simultaneous use of stimulants, psychedelics and a sedative. The following quote exemplifies a situation where a person combines a stimulant and a gabapentinoid to prolong a high and to alleviate negative symptoms:

“Sometimes I do Lyricas [pregabalin], I sniff them…the pills, after I do coke. It is a downer and the other, the coke, is an upper… I want Lyrica just to keep my buzz. [When] I wake up in the morning…I’m good this way, it’s cool, it’s quiet, I’m less anxious.”^{Footnote 32}

Discussion

We identified and summarized eight motivations of polysubstance use and their temporality of use. Building on previous reviews that looked more widely at polysubstance use,^{Footnote 10} our work intentionally puts a narrow focus on overlapping use and described preferred combinations based on the person’s experience and expectations of substance pharmacological effects.

Our results show that there are distinct motivations for using drugs sequentially and simultaneously in a single episode. The use of over five substances in an episode is common and preferred substances vary across groups,^{Footnote 14Footnote 15Footnote 43} making it difficult to capture general patterns of use.

While the object of our review was intentional polysubstance use, we acknowledge that substance combinations are not always a matter of choice. In illicit markets, preferred substances may be contaminated with other substances without the knowledge of the purchaser. In some instances, the progression and maintenance of use happen as a result of dependence, where the use of one substance triggers the use of another.^{Footnote 22} Other circumstantial factors can be at play; the emergence of new substances in the illegal local markets, the ease of access to traditional substances and price variations influence patterns of use.^{Footnote 44} When a substitute for a drug becomes cheaper, more available or of better quality, people will likely favour it. In North America, the increasing availability and quality of methamphetamine along with its decreased price have led to it being substituted for other stimulants^{Footnote 45Footnote 46} and to what has been described as the “twin epidemics” of methamphetamine and opioid use.^{Footnote 47} A similar pattern is currently being observed in Europe where cocaine quality and affordability have been steadily increasing and so has its use.^{Footnote 45}

The choice of substances that are used in combination also depends on the context in which they are used to fulfill specific functions.^{Footnote 44} For example, studies that include people who go to parties and bars tend to report combinations of “club drugs” including ecstasy/MDMA (methylenedioxymethamphetamine), amphetamines, ketamine, cocaine, GHB, psychedelics, cannabis and alcohol.^{Footnote 43Footnote 48Footnote 49} Club drugs are used to increase feelings of euphoria, desirability, self-insight and sociability.^{Footnote 50} In other cases, substance combinations can involve non-psychoactive substances that are used to improve the overall experience. For example, a beta blocker can be used to offset tachycardia or omeprazole to avoid stomach pain when using stimulants.^{Footnote 7} Studies that focus on people who are attracted to the same sex often describe the use of wide combinations of club drugs^{Footnote 15Footnote 51} along with erectile dysfunction medication and alkyl nitrite (or “poppers”) for sensation seeking, enhancing the sexual experience and fitting in.^{Footnote 52} Studies have also examined the use of prescription stimulants to enhance cognitive performance^{Footnote 28Footnote 53} and prescription drugs, including benzodiazepine and opioids, to alleviate distress among college and university students.^{Footnote 54Footnote 55}

Changes in the legal status of psychoactive substances are also expected to influence people’s behaviour. As a result of legislative changes, the use of synthetic cathinones such as mephedrone, which was very prevalent a few years ago,^{Footnote 35} has fallen drastically.^{Footnote 7} A similar pattern of substitution has been observed for fentanyl, where traditional opioids such as heroin were successively substituted with fentanyl and fentanyl analogs^{Footnote 56} and, more recently, with non-fentanyl analogs, with effects similar to fentanyl, and analogs such as the nitazenes.^{Footnote 57} Designer benzodiazepines such as etizolam are increasingly used as a replacement for their traditional counterparts.^{Footnote 58} These changes in the market are expected to be reflected in substance combinations.

While the effects of the new combinations of emerging substances are often unpredictable, analogs are designed to provide legal alternatives to controlled substances and often have similar effects.^{Footnote 7} Furthermore, the motivations for using and combining new substances remain similar to their classical counterparts;^{Footnote 59} hence the relevance of characterizing and monitoring typical patterns of polysubstance use based on the preferences of people who choose to combine substances.

Strengths and limitations

An important strength of this rapid review is its focal and targeted scope. We reviewed evidence on an explicit and narrow definition of polysubstance use, which allows for a better understanding of combinations potentially involved in acute toxicity events. We defined an episode within a period of 24 hours, but we acknowledge that an episode of use can take place over several days and even weeks.^{Footnote 60} Our review focused on articles published in the last decade to highlight patterns that may underlie the current overdose crisis. Qualitative data allowed us to create a richer portrait by characterizing the motivations for combining substances.

Certain limitations should be acknowledged. All included studies relied on self-reports that can be inaccurate because participants are not always aware of the content of a product, especially when using illegal substances.^{Footnote 61} We did not explore the mode of substance use, although this could be a determinant of expected effect. Furthermore, some relevant studies may not have been identified by our search strategy given the broad nature of the concept of polysubstance use; thus the combinations reported only represent an overview.

The context in which people use substances is known to influence their behaviour,^{Footnote 44} but published information on different settings with patterns of polysubstance use is limited. Finally, while no studies were excluded on the basis of sex/gender or identity of participants, the included work does not reflect the broad scope and diversity of experiences lived by people who use drugs.

Conclusion

While contextual factors such as changes in the illegal drug supply and availability of substance remain major drivers of behaviour, individual motivations significantly affect patterns of use. Putting a greater emphasis on the reasons why people choose to combine substances is a key factor in understanding polysubstance use patterns associated with higher risks of overdose. In doing so, we can better tailor harm reduction messaging to the complex reality of people who use substances.

Acknowledgements

We would like to thank Dominique Parisien, Amanda VanSteelandt, Margot Kuo, Sarah McDougall and Noushon Farmanara from the Public Health Agency of Canada for their assistance with protocol development and content review. We would also like to thank Lynda Gamble and Tanya Durr from the Public Health Agency of Canada Library, Ottawa, for their valuable assistance in the development of the search strategy.

Conflict of interest

The authors have no conflicts of interest to declare.

Authors’ contributions and statement

MBF – conceptualization of search strategy, screening of identified works for inclusion, data extraction, analysis and interpretation of data, and manuscript preparation

GC – data extraction, analysis and interpretation of data, and manuscript preparation

GG – data extraction, analysis and interpretation of data, and manuscript preparation

CL – review of search strategy, screening of identified works for inclusion, analysis and interpretation of data, and manuscript preparation

The content and views expressed in this article are those of the authors and do not necessarily reflect those of the Government of Canada.

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