Cognitive and neurobiological factors

Addiction has been conceptualised as a chronic relapsing disorder comprising three stages: binge/intoxication, withdrawal/negative affect and preoccupation/anticipation, which correspond to distinct brain structures and circuits. ^{Reference Koob and Volkow22} During the binge/intoxication stage, the positive and rewarding effects of drugs are experienced. While AASs do not induce a typical intoxication syndrome, people using AASs frequently report feelings of mild euphoria and invincibility. ^{Reference Pope and Katz23,Reference Pope and Katz24} Similarly, animal models suggest that reward circuitry implicated in addiction is also affected by AAS use. ^{Reference Wood25,Reference Scarth and Bjørnebekk26} AASs also differ from most psychoactive drugs in that they do not usually cause acute impairments in coordination, perception or cognition, and therefore do not require the same level of regulation with respect to tasks such as driving, compared to substances like alcohol or opioids. This may partially explain why individuals evaluated for AAS dependence or AASUD infrequently report failing to fulfil social or occupational obligations because of use. ^{Reference Ganson, Hallward, Cunningham, Murray and Nagata27–Reference Scarth, Westlye, Havnes and Bjørnebekk29}

The withdrawal/negative affect stage begins when substance use is ceased or reduced, and people with dependence will experience symptoms of withdrawal, including increased irritability and anxiety. Withdrawal symptoms can vary depending on the substance, with withdrawal from psychoactive substances resulting from central nervous system adaptations, leading to both neuropsychiatric and physical symptoms. For example, opioid withdrawal may include fever, nausea and vomiting, excessive sweating and yawning, as well as increased anxiety, irritability and insomnia. ³⁰ People using AASs often report withdrawal symptoms; however, these symptoms are largely driven by the endocrine system, particularly the hypothalamic–pituitary–gonadal (HPG) axis, in addition to neuropsychiatric effects related to the autonomic nervous system.

The acute phase of AAS withdrawal can include sympathetic activation with symptoms of headache, palpitations and nausea. ^{Reference Brower31} In addition, AASs are distinct from non-hormonal drugs in their impact on endogenous hormone production, which can lead to enduring withdrawal symptoms. The administration of supraphysiological doses of androgens suppresses the release of key reproductive hormones, leading to reduced endogenous testosterone production caused by a negative feedback mechanism within the HPG axis, known as hypogonadism. This negative feedback loop is intensified by high levels of oestrogens resulting from aromatisation of exogenous AASs. These changes to the HPG axis contribute to symptoms of testosterone deficiency when AAS use has ceased, including fatigue, erectile dysfunction, depression and low libido. ^{Reference Sharma, Grant, Islam, Kapoor, Pradeep and Jayasena8} While hypogonadism is also highly prevalent among individuals using opioids, it is not directly related to the development of opioid use disorder, highlighting the unique role of hormonal dysregulation in AAS withdrawal and its distinct impact on the motivation to continue using. Notably, in preliminary research we have seen that women report symptoms of withdrawal less often than men, which may be explained by lower endogenous testosterone levels in women and should be taken into consideration in clinical evaluations. ^{Reference Scarth, Havnes, Jørstad and Bjørnebekk20}

Finally, the preoccupation/anticipation stage is characterised by craving a substance and involves executive functions, including impulse control, which are mediated by structures such as the prefrontal cortex. Deficits in executive function and attention are highly prevalent among people with SUD, leading to challenges such as poor impulse inhibition, emotion regulation and decision-making. ^{Reference Gustavson, Stallings, Corley, Miyake, Hewitt and Friedman32–Reference Verdejo-Garcia, Garcia-Fernandez and Dom34} These functions are critical to inhibiting craving, which was added to the DSM-V as a SUD symptom. To our knowledge, two studies have used this criteria to evaluate AASUD, finding that 27.9% and 42.7%, respectively, of people reporting AAS use experienced craving, which was the most commonly reported AASUD symptom in both studies. ^{Reference Ganson, Hallward, Cunningham, Murray and Nagata27,Reference de Zeeuw, Brunt, van Amsterdam, van de Ven and van den Brink28} In addition, a recent study evaluating an AAS craving scale identified underlying aspects of craving, including expectation, environment and mood. ^{Reference Zoob Carter and Boardley14} These findings may contribute to a deeper understanding of this symptom in the context of AAS use, which has its own distinct environment and use patterns.

Interestingly, people with AAS dependence often exhibit similar patterns of executive dysfunction relative to other SUDs, including compromised impulse inhibition, working memory and emotional control. ^{Reference Hauger, Westlye and Bjørnebekk35,Reference Scarth, Havnes, Jørstad, McVeigh, Van Hout and Westlye36} In addition, brain imaging studies have identified a thinner cortex in prefrontal regions associated with inhibitory control, ^{Reference Hauger, Westlye, Fjell, Walhovd and Bjørnebekk37} and signs of accelerated brain ageing in frontal regions among people with AAS dependence relative to controls, ^{Reference Bjørnebekk, Kaufmann, Hauger, Klonteig, Hullstein and Westlye38} a pattern also often observed in other drug dependencies. ^{Reference Mackey, Allgaier, Chaarani, Spechler, Orr and Bunn39,Reference Scheffler, Ipser, Pancholi, Murphy, Cao and Ottino-González40}

Psychiatric comorbidities

SUDs are frequently comorbid with other psychiatric conditions. It is difficult to determine the direction of this relationship, as early mental illness may contribute to problematic substance use, or substance use may contribute to the development of mental illness. Furthermore, it may also be the case that there are shared underlying vulnerabilities for multiple disorders. Regardless, it is clear that there is a higher prevalence of psychiatric disorders, including depression, anxiety, post-traumatic stress disorder, attention-deficit hyperactivity disorder (ADHD) and several personality disorders, including antisocial and borderline, among people with SUD compared to the general population. ^{Reference Santo, Campbell, Gisev, Martino-Burke, Wilson and Colledge-Frisby41,Reference Grant, Saha, Ruan, Goldstein, Chou and Jung42}

Similarly, AAS use and dependence have been associated with a number of psychiatric conditions, many of them overlapping with those observed in other SUD populations. These include ADHD, anxiety, depression and several personality disorders, including antisocial, paranoid and borderline (now called emotionally unstable personality disorder in the ICD-11). ^{Reference Scarth, Havnes, Jørstad, McVeigh, Van Hout and Westlye36,Reference Jørstad, Scarth, Torgersen, Pope and Bjørnebekk43–Reference Ip, Lu, Barnett, Tenerowicz, Vo and Perry46} In addition, it is important to highlight the role of body dysmorphia, in particular muscle dysmorphia, among people using AASs. People with these body image concerns are more likely to use AASs and other supplements or behaviours that put their health at risk in the pursuit of improving musculature and appearance. ^{Reference Scarth, Westlye, Havnes and Bjørnebekk29,Reference Murray, Griffiths, Mond, Kean and Blashill47,Reference Kanayama, Pope and Hudson48} Furthermore, social physique anxiety and fears of losing muscle mass may prolong AAS use and increase the severity of AAS dependence. ^{Reference Griffiths, Jacka, Degenhardt, Murray and Larance49}

Motivation and social context

The motivation to use AASs differs from other substances, as AASs are most often used to achieve a long-term physique or performance goal. AASs are usually one component of a structured regimen involving rigorous training and adherence to a strict diet. This goal-driven mindset contrasts with classical psychoactive drugs, where use is often driven by immediate gratification, either seeking euphoria, or relief of pain, stress or emotional discomfort. ^{Reference Biolcati and Passini50} This distinction in motivational forces is likely also one reason why people who use AASs may not identify with SUD patients. ^{Reference Santos and Coomber51} However, these groups likely share underlying vulnerabilities, such as low self-esteem and cognitive, genetic and environmental factors, as described previously.

Understanding the distinction in motivational forces is critical, as these variations may inform barriers to seeking treatment. The long-term focus and structured, intentional use of AASs may make it more difficult for individuals using these substances to recognise when the negative health effects overshadow the positive ones. Many people who use AASs are striving to achieve an ‘ideal’ physique that is perceived as optimal within certain communities, making it challenging to cease use and seek treatment, even when the adverse effects become concerning to the individual.

The social and physical environment in which AASs are used differ substantially from those associated with psychoactive drugs like alcohol or opioids. While social conformity can play a role in all types of addictions, it is important for health professionals to be aware of the specific context in which AASs are used. Use of AASs can be closely tied to subcultures such as the gym culture and/or bodybuilding communities. Within these environments, AAS use might be normalised as a legitimate part of a typical training regime aimed at enhancing muscle mass and physical appearance. ^{Reference Kimergård52} In addition, AASs are often used in conjunction with other appearance and performance-enhancing drugs, including stimulants, insulin, growth hormones and drugs taken to reduce fat, such as clenbuterol.

AAS use may also be driven by societal pressure to adhere to traditional ideals of masculinity, or to fend off ageing that men may attribute to declining testosterone levels. ^{Reference Greenway and Price53,Reference Gagliano-Jucá, Alvarez and Basaria54} These social contexts and environments can distinguish AAS users from those using substances like 3,4-methylenedioxymethamphetamine (MDMA) or heroin and may contribute to their reluctance to identify with or seek treatment in facilities primarily designed for other SUDs.

However, while not the primary population using AASs, a high prevalence of AAS use has been reported among people in SUD treatment (28%), which may be explained by specific motivations, including a desire to regain weight and muscle mass following prolonged use of opioids or stimulants. ^{Reference Havnes, Jørstad, McVeigh, Van Hout and Bjørnebekk55} Furthermore, several shared risk factors, including adverse childhood experiences, ADHD and certain personality disorders, may explain the significant overlap between AAS use and other substance use.

Diagnostic considerations

There is strong evidence that AAS use can lead to both physical and psychological dependence, underscoring the need for a specific diagnostic category for AASUD. While AASUD shares many cognitive, neurobiological and psychiatric features with other SUDs, there are unique challenges that warrant specific clinical attention. Unlike typical psychoactive substances, AASs directly affect the endocrine system, disrupting reproductive hormones and often resulting in reduced or absent testosterone production. Establishing specific diagnostic criteria for AASUD will enhance healthcare professionals’ awareness and understanding of the disorder, as well as the unique challenges faced by patients. This is a particularly critical point, as people using AASs often perceive doctors to lack competence in AAS knowledge, and subsequently prefer self-treatment methods along with advice from peers. ^{Reference Pope, Kanayama, Ionescu-Pioggia and Hudson56,Reference Cox, Piatkowski and McVeigh57}

Figure 1 summarises important points for diagnostic criteria for AASUD. Both the ICD and DSM should include information about AASUD, including its association with body image pathologies and the unique social and environmental contexts in which AASs are used. Descriptions of withdrawal symptoms should highlight the impact of AASs on the HPG axis and reproductive hormones. Gender differences should also be mentioned, particularly that women may not experience withdrawal symptoms to the same extent as men, but may face additional stigma and shame associated with AAS use.

Fig. 1 Recommendations for AASUD diagnostic classification.

Finally, the relevance of failing to fulfil social or occupational obligations because of use should be carefully considered for AASUD, as AASs do not inhibit people using them to the same extent as other types of drugs, and this symptom often has low prevalence among people reporting AAS use. With these considerations, healthcare providers will be better equipped to recognise, diagnose and treat AASUD, with significant benefits for patients.