Despite decades of research on amphetamine derivatives, a class of compounds sharing a structural foundation with amphetamine, crucial gaps remain in our understanding of these drugs in a variety of animal species and humans. This dissertation addresses three of these gaps through a multi-level approach involving studies in both humans and mice. Specifically, it focuses on investigating the lack of information regarding: 1) repeated dosing of 3,4-methylenedioxymethamphetamine in humans, 2) methamphetamine/alcohol combinations in humans and 3) methamphetamine/oxycodone combinations in mice. Study 1 involved administering three consecutive doses of 3,4 methylenedioxymethamphetamine to human volunteers at 12- and 24-hour intervals while physiological, behavioral, and subjective measures were collected. Study 2 reanalyzed Kirkpatrick and colleagues (2012a) data to evaluate repeated administrations of methamphetamine and alcohol. The reanalysis focused on quantifying the physiological and subjective effect differences between the first and second administrations, which occurred at a 12-hour interval on the same day, an aspect not previously analyzed or reported by the original authors. Study 3 utilized well-established animal models such as Conditioned Place Preference, Open Field Test, and Novel Object Recognition to evaluate the reward-like and aversive effects of methamphetamine and oxycodone combinations in mice. Study 1 was the first to quantify the effects of multiple 3,4-methylenedioxymethamphetamine doses administered over a 36-hour period of time. Initially, acute 3,4-methylenedioxymethamphetamine produced dose-dependent increases in peak heart rate, blood pressure, and more positive than negative subjective effects. However, by the third dose, many of these effects dissipated, heart rate was no longer elevated, and residual mood effects were minor. Overall, the data do not support the general perception that 3,4-methylenedioxymethamphetamine produces dangerous cardiovascular and residual mood effects in humans following repeated administration. The results of Study 2, again a first in the field, discovered that contrary to expectations, heart rate increases produced by the methamphetamine/alcohol combination were not further increased with repeated dosing, but rather attenuated. In fact, methamphetamine offset alcohol-induced intoxication, even after repeated administration. Study 3 revealed that combining methamphetamine and oxycodone in mice increased reward as measured by Conditioned Place Preference, but not more than either drug alone. However, methamphetamine lengthened the duration of Conditioned Place Preference for the lower oxycodone dose and offset the oxycodone-induced disruptions in novel object recognition performance. One crucial cross-species observation was that methamphetamine mitigated adverse effects such as alcohol-related intoxication and oxycodone cognitive disruption, even after repeated administration. While seemingly beneficial, this observation raises concerns that individuals who combine these drugs may be at risk of underestimating their overall degree of impairment, potentially leading to hazardous activities like driving while intoxicated or engaging in risky behaviors. Sharing this insight is crucial to encourage informed, responsible behavior and safeguard public safety. In conclusion, these studies have significantly enhanced our understanding of two frequently used amphetamine derivatives and their interactions with two commonly used psychoactive drugs—oxycodone and alcohol. Most importantly, we strongly advocate for robust empirical experimentation to counteract misinformation related to 3,4-methylenedioxymethamphetamine and methamphetamine. These endeavors are crucial for developing more precise assessments of the risks and benefits associated with these substances, and for improving drug policies and optimizing public health interventions.

The pandemic of alcohol and drug abuse continues to ravage families, communities and societies placing many households, even communities, under siege. For persons living in an addictive home it is like living in a whirlwind where a family member’s substance use disorder (SUD) turns homes into sporadic unpredictable and out-of-control environments. The partner or concerned significant other (CSO) of the partner with the SUD becomes so engrossed in the latter, that they sacrifice their own time, needs, energies and resources to manage the whirlwind, even adopting maladaptive coping skills to survive. When partners with SUDs begin treatment, its modalities primarily focus on treating the partner with the SUD. The non-abusing CSO-partner is mostly conceptualised as an adjunct treatment collaborator for partners with a SUD and therefore instrumental to a successful treatment outcome. The CSO-partner’s own needs for professional treatment go unattended while they themselves seldom receive specialised treatment to heal and recover from the many and varied scars caused by the whirlwind of a partner’s SUD. They are thus deprived of a service to which they are entitled in their own right. This explains a lacuna in home-grown treatment which falls within the ambit of social work for a CSO-partner. Utilising a qualitative research approach, and the collective instrumental case study and phenomenological research designs complemented by an explorative, descriptive and contextual strategy of inquiry, I explored the experiences, challenges and coping strategies of CSOs living with a partner with a SUD with the view of informing guidelines for social work intervention from 12 CSO-partners and their partners with a SUD. These guidelines were informed by their suggestions for social work support. To live with a partner with a SUD was for all the CSO-participants an overall negative and stressful experience in which they felt isolated and trapped. Feelings of anger and frustration; sadness; embarrassment; shame, humiliation; despair, and hopelessness were experienced causing some of them to emotionally disengage from their partners. Their partners’ SUD-related behaviour had a negative effect on them; their relationships and the relationships with their children. The partner’s argumentative attitudes; intimate partner violence; lack of responsibility; erratic, reckless behaviour, manipulation and threatening relapse were highlighted as some of the challenges experienced. A mix of coping strategies that can be categorised as both adaptive and maladaptive, or enabling behaviours, were employed to mitigate and manage the challenges experienced. The CSO-participants also employed external sources of motivation to convince or force their partners to enter treatment. Admitting to the fact that their SUD’s had affected the CSO-partners negatively, both the partners with the SUDs and their CSO-partners offered suggestions for social work support for the CSOs of partners with a SUD. Topics to be covered during social work interventions to support to CSOs included providing information about drugs and its effects; setting of boundaries and personal safety; rebuilding self-esteem; anger-management; relapse management; and parenting and marriage counselling. Ways in which to provide such social work intervention and support suggested was through couple counselling; family counselling and support groups, and a tailor-made programme catering specifically for the CSO-partners. Based on the research findings, guidelines were formulated as recommendations for social work intervention directed at social work practice. Additional recommendations for education and training; continuous professional development, and ideas for future research were also suggested. / Social Work / D. Phil. (Social Work)