ABSTRACT
Psychoactive substances obtained from botanicals have been applied for a wide variety of purposes in the rituals of different cultures for thousands of years. Classical psychedelics from N,N'-dimethyltryptamine, psilocybin, mescaline and various lysergamides cause specific alterations in perception, emotion and cognition by acting through serotonin 5-HT2A receptor activation. Lysergic acid diethylamide, the first famous breakthrough in the field, was discovered by chance by Albert Hoffman in the Zurich Sandoz laboratory in 1943, and studies on its psychoactive effects began to take place in the literature. Studies in this area were blocked after the legislation controlling the use and research of psychedelic drugs came into force in 1967, but since the 1990s, it has started to be a matter of scientific curiosity again by various research groups. In particular, with the crucial reports of psychotherapy-assisted psilocybin applications for life-threatening cancer-related anxiety and depression, a new avenues have been opened in the treatment of psychiatric diseases such as treatment-resistant depression and substance addictions. An increasing number of studies show that psychedelics have a very promising potential in the treatment of neuropsychiatric diseases where the desired efficiency cannot be achieved with conventional treatment methods. In this context, we discuss psychedelic therapy, encompassing its historical development, therapeutic applications and potential treatment effects-especially in depression, trauma disorders and substance use disorders-within the framework of ethical considerations.
ABSTRACT
The delayed onset of monoaminergic antidepressants and disadvantages of traditional administration routes created the need for alternative non-invasive delivery methods with rapid onset therapeutic effect. Ketamine attracted attention as a fast-acting glutamatergic antidepressant with ideal physiochemical properties for alternative routes of administration. However, there is no sufficient data for its transdermal use in depression. In this proof-of-concept study, we investigated the antidepressant effects of transdermal ketamine delivered via a novel ointment with skin protective, emulsifying and permeation enhancing properties. A shea butter-based 5% (w/w) ketamine ointment or a drug-free vehicle ointment were applied to the shaved dorsal skin of male Wistar rats for 2 days, twice a day. Behavioral despair, locomotor activity and anxiety-like behavior were respectively assessed in the forced swim test (FST), open field test (OFT), and elevated plus maze (EPM). The pharmacokinetic profile of the ointment was analyzed with high-performance liquid chromatography. Transdermal ketamine ameliorated behavioral despair without altering general locomotor activity and anxiety-like behavior, showing that skin-friendly drug carriers like shea butter may constitute promising alternatives to current routes of delivery for ketamine. Tested transdermal method aims to provide more sustainable drug delivery for long-term treatment schedules. Future studies can investigate its long-term use, side effects and abuse liability.
