Background: Drugs primarily affect the way individuals think, feel and behave with regard to the world around them. Illicit substances such as crystal methamphetamine show a strong association to abnormalities in the process of neurotransmission. Objective: The main aim of this review is to analyse substance abuse and abnormalities in neurotransmission focusing on crystal methamphetamine and its physiological, psychological and social implications. Methods: An extensive systematic electronic review (EBSCOhost, JSTOR, ProQuest Science, Science Direct, Research Gate, Google Scholar and PubMed) were used. Research articles and books were searched using the keywords ‘effects of crystal methamphetamine’, ‘neurotransmission in substance abuse’, ‘substance abuse by homosexual males’. Discussion and Conclusion: This thematic review draws close attention to the physiological changes, psychological disorders and abuse of crystal methamphetamine among homosexual men tested positive for Human Immunodeficiency Virus (HIV) as well as a need for better health social care services and treatment in order to overcome homophobic stigmatization.