One promising approach relies on a big data approach of developing predictive models by computational mining of datasets related to drug abuse [97]. This approach has the potential to discover novel mechanisms of synergy by identifying common target proteins and convergent signaling pathways. As this is a relatively new approach, its utility will depend on the breadth of the database and sophistication of the computational tools, both of which will evolve with time. The complex rewarding effects of nicotine are mediated by multiple receptors in the VTA and NAC, although its actions at the β2-nAChR subtype are considered to be integral to the rewarding effects [83].
Accordingly, further studies will be needed to investigate PSA patterns in adolescents. PUD is a medical condition that develops from long-term use or misuse of 2 or more substances. PUD includes use of a drug such as cocaine or misuse of alcohol, tobacco, or a prescription medicine such as opioids. This section explores the various components of doing this, from screening for multiple substance use and mental health disorders, to treatment options, and the use of team-based care.
- All psychostimulants directly enhance striatal DA release via disruption of dopamine transporter (DAT) activity (Pontieri et al., 1995), though they do so via distinct mechanisms.
- Unlike psychostimulants and nicotine, however, long-term exposure to opioids decreases dendritic branching and spine density in NAc MSNs and mPFC pyramidal cells (Badiani et al., 1999; Robinson et al., 2002; Van Den Oever et al., 2008).
- For example, chronic pretreatment with nicotine enhances acute alcohol-induced DA release in the NAc (Johnson et al., 1995; Blomqvist et al., 1996), and elevated levels of DA, DOPAC, and HVA persist for over an hour (Tizabi et al., 2002, 2007; Ding et al., 2012).
- This leads to an increased risk of overdose because the user doesn’t accurately feel the effects that the drugs are having on their body.
- Additionally, sex differences can be used as a tool to elucidate the neurobiological mechanisms underlying polysubstance abuse.
- Combining two substances such as this can mask the effects of each, making identifying the specific drug of abuse more challenging.
For instance, it’s imperative to identify whether substance use disorders will be treated concurrently or independently, and what other professionals may be part of the care team. Because polysubstance abuse involves using multiple drugs, the first step in treatment is detoxification. Healthcare providers often supervise this process to manage and alleviate withdrawal symptoms. Generally, people should not take stimulants (like Adderall) with other substances unless directed by their healthcare provider.
Combining two substances such as this can mask the effects of each, making identifying the specific drug of abuse more challenging. In addition to acute actions described above, all drugs of abuse produce long-term plasticity that contributes to compulsive behaviors that characterize substance use disorder. They do so through multiple mechanisms, and a description of this is beyond the scope of this Perspective. However, a shared mechanism through which most drugs of abuse induce enduring neuroadaptations is by increasing the AMPAR/NMDAR ratio, resulting in enhanced excitatory transmission onto VTA-DA neurons [70, 94]. The mechanisms by which individual drug classes produce their effects and whether these are specific to individual classes is a topic of future investigation.
Despite its widespread use, much less is known about the mechanisms underlying the acute effects of alcohol. Alcohol activates dissociated VTADA neurons (Brodie et al., 1999) and induces DA release into the NAc (Weiss et al., 1993; https://sober-house.net/ Pontieri et al., 1996; Lecca et al., 2006), similar to other potentially addictive drugs. However, GABAA receptors are known to play a central role in the effects of alcohol (Hyytiä and Koob, 1995; Lobo and Harris, 2008).
Polysubstance abuse and prescription drugs
This may trick you into thinking that the drugs are not affecting you, making it easier to overdose. If you are admitted to a medical detox center, you will receive 24-hour supervision from healthcare professionals. They will be able to monitor your vital signs continually and administer prompt treatments for medical emergencies that arise. Lastly, health professionals may also consider polysubstance use as a substance use disorder. In these cases, they may refer to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association. When a person consumes drugs, physiological changes occur, both mentally and physically, to produce possible dependence, tolerance, and intensified cravings.
Learn more about Polysubstance Use Disorder
In general, it is recommended to offer medications for each individual substance use disorder in addition to psychosocial support. Per The Department of Veterans Affairs (VA) and the Department of Defense (DoD) SUD treatment guidelines,36 there is insufficient evidence to recommend for or against pharmacotherapy for the treatment of cocaine use disorder or methamphetamine use disorder. If medications for stimulant use disorders are being considered the following should be considered. In addition to initial screening for drug and alcohol use, ongoing monitoring of drug and alcohol use is recommended when people are in treatment for substance use and other mental health disorders. We also highlight the potential importance of careful translation of preclinical research to human studies.
For example, chronic pretreatment with nicotine enhances acute alcohol-induced DA release in the NAc (Johnson et al., 1995; Blomqvist et al., 1996), and elevated levels of DA, DOPAC, and HVA persist for over an hour (Tizabi et al., 2002, 2007; Ding et al., 2012). Additionally, alcohol and nicotine co-administration acutely increase production of BDNF and GDNF in the NAc (Truitt et al., 2015), along with increases in glutamatergic signaling in the VTA and PFC (Deehan et al., 2015; Engle et al., 2015). Notably, this wide activation of the C-BG-T network is absent following administration of either drug alone, demonstrating a unique mechanism of action for alcohol and nicotine polydrug use. The striatum is a heterogeneous structure comprised primarily of two interspersed populations of GABAergic medium spiny neurons (MSNs) that can bidirectionally regulate behavioral output. Direct pathway MSNs (dMSNs) express dopamine D1-like (D1) receptors and the neuropeptides dynorphin and substance P, project directly to the midbrain, and can promote behavioral output by serving as a “go” signal. Conversely, indirect pathway MSNs (iMSNs) express dopamine D2-like (D2) receptors and the neuropeptide enkephalin, project indirectly to the midbrain via the pallidum (GPe and VP), and can suppress behavioral actions by serving as a “stop” signal (Kravitz et al., 2010; Gerfen and Surmeier, 2011).
Patterns of opioid consumption and progression vary according to sex and gender and detailed analysis of these patterns for polysubstance use are needed as well to optimize individualized strategies for prevention and treatment. Additionally, sex differences can be used as a tool to elucidate the neurobiological mechanisms underlying polysubstance abuse. While the focus of this Perspective is on polysubstance use in the context of opioids, it is important to consider that polysubstance use frequently occurs with all recreational drugs, whether their use is legal can you drink alcohol on prednisolone or illegal. Marijuana users are far more likely to use opioids nonmedically than people who do not use marijuana. Further, as a general principal, the more widely a drug is used, the higher the percentage of users who do not use other drugs; and, the less widely used, the more likely a drug is to be used with other drugs (Fig. 1). While the reasons for this increasing overlap in substances that are less frequently consumed is not totally clear, some of it may relate to the drug use trajectories where substances are added to one another in a progression.
Effects of Polydrug Use on Addictive Behaviors
As of 2014, 7.9 million people had a co-occurring mental disorder and substance use disorder, NAMI reports. Treating co-occurring disorders can be more challenging, as it’s important that both disorders are properly diagnosed and treated or a person’s recovery outcome may be affected. With the support and guidance of a professional treatment program, it is possible to overcome a polysubstance use disorder. Addiction also impacts the brain region responsible for anxiety, irritability and unease. These symptoms often accompany withdrawal, thus motivating a person to seek the drug again.
Offer concurrent substance use treatment
In its parks, under railroad overpasses and here in the woods, people ensnared by drugs scramble to survive. Dr. Helmstetter, who makes weekly primary care rounds with a program called Street Medicine Kalamazoo, carried medications to reverse overdoses, blunt cravings and ease withdrawal-induced nausea. Always let your doctor know what drugs you are taking to prevent any adverse reactions with newly prescribed medications. Unintentional polysubstance use occurs when a person takes drugs that have been mixed or cut with other substances, like fentanyl, without their knowledge. Intentional polysubstance use occurs when a person takes a drug to increase or decrease the effects of a different drug or wants to experience the effects of the combination. This includes when two or more are taken together or within a short time period, either intentionally or unintentionally.
Studies of polysubstance use with this combination find increased death rates, with 20% or more of people who died found to be using both drug types. Both drugs act on areas of the brain that cause them to suppress a person’s ability to breathe, with a stronger effect when taken together. While a medical detox may be the necessary first phase of addiction treatment, a formal treatment program should always follow detox to ensure the best chance for a successful recovery outcome, especially in the case of polysubstance abuse and addiction.
Fortunately, a holistic and individualized treatment plan can help you safely detox and begin a healthier, happier life free from substance use. Continue reading to learn more about the signs and dangers of polysubstance misuse and how to get help. While fully integrated treatment for co-occurring disorders is the ideal, not all clinics will be able to provide this level of care. Thus, building out networks of community specialists to refer to and coordinate care with should be done. This will take time and effort to develop and maintain and support the necessary level of care coordination around treatment goals. Therefore, the best treatment for polysubstance use is optimizing and focusing treatment efforts on the substances we have the most effective treatments for, as opposed to focusing on substances we have less effective treatments for, like benzodiazepines and stimulants.
However, these models are limited in their capacity to fully encompass the complex social and environmental contexts that contribute to the unique use patterns for multiple substances with addiction potential. Nevertheless, when designing experiments in clinical or preclinical populations, factors such as time of day of intake, temporal proximity of intake, and environmental preferences for administration must be consideredfor each substance class. For instance, cocaine use is predominantly favored outside of home environments, whereas heroin use is greater in “home” contexts in both humans and rodents (Caprioli et al., 2009; Badiani and Spagnolo, 2013; De Pirro et al., 2018; De Luca et al., 2019).
